Table of SynGAP1 Isoform α2 (UniProt Q96PV0-1) Missense Variants.

c.dna	Variant	SGM Consensus	Domain and Structure information: based on WT protein												Annotated databases						Deep learning-based pathogenicity predictions					Folding stability-based pathogenicity predictions									Sequence/structure-based pathogenicity predictions														Phase Separation			Evolutionary/physical properties				Molecular Dynamics-based analysis															DOI
			Domain	IUPred2		ANCHOR2		AlphaFold		MobiDB	PhosphoSitePlus				ClinVar			gnomAD			ESM1b		AlphaMissense			FoldX			Rosetta		Foldetta		PremPS		REVEL		PROVEAN		PolyPhen-2 HumDiv		PolyPhen-2 HumVar		FATHMM		SIFT				PSMutPred			PAM		Physical		SASA		Normalized B-factor backbone		Normalized B-factor sidechain		SynGAP Structural Annotation
				Score	Prediction	Score	Prediction	pLDDT	disorder	disorder	LTP	HTP	KL	PTM	Clinical Status	Review	Subm.	ID	Allele count	Allele freq.	LLR score	Prediction	Pathogenicity	Class	Optimized	Average ΔΔG	Prediction	StdDev	ΔΔG	Prediction	ΔΔG	Prediction	ΔΔG	Prediction	Score	Prediction	Score	Prediction	pph2_prob	Prediction	pph2_prob	Prediction	Nervous System Score	Prediction	Prediction	Status	Conservation	Sequences	IP RF	SP RF	Prediction	PAM250	PAM120	Hydropathy Δ	MW Δ	Average	Δ	Δ	StdDev	Δ	StdDev	Secondary	Tertiary bonds	Inside out	GAP-Ras interface	At membrane	No effect	MD Alert	Verdict	Description
c.3838A>T	M1280L 2D AIThe SynGAP1 missense variant M1280L is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, AlphaMissense‑Optimized, and ESM1b. Tools that predict a pathogenic effect are SIFT and FATHMM. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; the Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of evidence points to a benign impact. The predictions do not contradict any ClinVar status, as no ClinVar claim exists for this variant. Thus, based on current computational predictions, the M1280L variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.882776	Disordered	0.822030	Binding	0.510	0.726	0.875											-1.391	Likely Benign	0.092	Likely Benign	Likely Benign										0.204	Likely Benign	-2.23	Neutral	0.052	Benign	0.017	Benign	2.40	Pathogenic	0.00	Affected			0.1113	0.3186		4	2	1.9	-18.03
c.3840G>A	M1280I 2D AIThe SynGAP1 missense variant M1280I is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 (HumDiv and HumVar), AlphaMissense‑Default, AlphaMissense‑Optimized, and ESM1b. Tools that predict a pathogenic effect are PROVEAN, SIFT, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic), and Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.882776	Disordered	0.822030	Binding	0.510	0.726	0.875											-3.723	Likely Benign	0.251	Likely Benign	Likely Benign										0.166	Likely Benign	-2.59	Deleterious	0.059	Benign	0.041	Benign	2.35	Pathogenic	0.00	Affected			0.0995	0.2468		2	1	2.6	-18.03
c.3840G>C	M1280I 2D AIThe SynGAP1 missense variant M1280I is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 (HumDiv and HumVar), AlphaMissense‑Default, AlphaMissense‑Optimized, and ESM1b. Tools that predict a pathogenic effect are PROVEAN, SIFT, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic), and Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.882776	Disordered	0.822030	Binding	0.510	0.726	0.875											-3.723	Likely Benign	0.251	Likely Benign	Likely Benign										0.166	Likely Benign	-2.59	Deleterious	0.059	Benign	0.041	Benign	2.35	Pathogenic	0.00	Affected			0.0995	0.2468		2	1	2.6	-18.03
c.3840G>T	M1280I 2D AIThe SynGAP1 missense variant M1280I is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 (HumDiv and HumVar), AlphaMissense‑Default, AlphaMissense‑Optimized, and ESM1b. Tools that predict a pathogenic effect are PROVEAN, SIFT, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic), and Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.882776	Disordered	0.822030	Binding	0.510	0.726	0.875											-3.723	Likely Benign	0.251	Likely Benign	Likely Benign										0.166	Likely Benign	-2.59	Deleterious	0.059	Benign	0.041	Benign	2.35	Pathogenic	0.00	Affected			0.0995	0.2468		2	1	2.6	-18.03
c.3G>A	M1I 2D AIThe SynGAP1 missense variant M1I is listed in ClinVar (ID 833646.0) with an uncertain significance annotation and is not reported in gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM all classify the substitution as benign, while SIFT uniquely predicts it to be pathogenic. The consensus score from the SGM framework, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign outcome. High‑accuracy predictors are incomplete: AlphaMissense‑Optimized and the Foldetta stability assessment are unavailable for this variant. Taking the collective evidence into account, the variant is most likely benign, and this assessment does not conflict with the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.642678	Disordered	0.540766	Binding	0.354	0.924	0.875					Conflicting		3				-5.397	Likely Benign													0.227	Likely Benign	-0.17	Neutral	0.001	Benign	0.000	Benign	4.25	Benign	0.00	Affected	4.32	1	0.1655	0.4008		2	1	2.6	-18.03
c.46A>C	M16L 2D AIThe SynGAP1 missense variant M16L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Based on the collective evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is provided). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.440853	Structured	0.459925	Uncertain	0.346	0.908	0.375											-1.277	Likely Benign	0.249	Likely Benign	Likely Benign										0.075	Likely Benign	-0.33	Neutral	0.001	Benign	0.000	Benign	4.37	Benign	0.00	Affected			0.1805	0.4629		4	2	1.9	-18.03
c.46A>T	M16L 2D AIThe SynGAP1 missense variant M16L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.440853	Structured	0.459925	Uncertain	0.346	0.908	0.375											-1.277	Likely Benign	0.249	Likely Benign	Likely Benign										0.075	Likely Benign	-0.33	Neutral	0.001	Benign	0.000	Benign	4.37	Benign	0.00	Affected			0.1805	0.4629		4	2	1.9	-18.03
c.48G>A	M16I 2D AIThe SynGAP1 missense variant M16I is listed in ClinVar with an “Uncertain” status (ClinVar ID 1424213.0) and is present in gnomAD (6‑33420312‑G‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact, and this is consistent with the ClinVar “Uncertain” designation rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.440853	Structured	0.459925	Uncertain	0.346	0.908	0.375					Uncertain		1	6-33420312-G-A	1	6.49e-7	-2.198	Likely Benign	0.722	Likely Pathogenic	Likely Benign										0.057	Likely Benign	-0.15	Neutral	0.000	Benign	0.000	Benign	4.28	Benign	0.00	Affected	4.32	1	0.1606	0.3877		2	1	2.6	-18.03
c.48G>C	M16I 2D AIThe SynGAP1 missense variant M16I is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of computational predictions and the high‑accuracy consensus suggest that M16I is most likely benign, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.440853	Structured	0.459925	Uncertain	0.346	0.908	0.375											-2.198	Likely Benign	0.722	Likely Pathogenic	Likely Benign										0.057	Likely Benign	-0.15	Neutral	0.000	Benign	0.000	Benign	4.28	Benign	0.00	Affected	4.32	1	0.1606	0.3877		2	1	2.6	-18.03
c.48G>T	M16I 2D AIThe SynGAP1 missense variant M16I is not reported in ClinVar (ClinVar ID = None) but is present in gnomAD (ID = 6‑33420312‑G‑T). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of computational evidence points to a benign impact, and this is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.440853	Structured	0.459925	Uncertain	0.346	0.908	0.375								6-33420312-G-T			-2.198	Likely Benign	0.722	Likely Pathogenic	Likely Benign										0.057	Likely Benign	-0.15	Neutral	0.000	Benign	0.000	Benign	4.28	Benign	0.00	Affected	4.32	1	0.1606	0.3877		2	1	2.6	-18.03
c.520A>C	M174L 2D AIThe SynGAP1 missense variant M174L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Only AlphaMissense‑Default predicts a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Taken together, the majority of evidence points to a benign impact for M174L. This conclusion is consistent with the lack of ClinVar annotation and does not contradict any existing clinical classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.661982	Disordered	0.485854	Uncertain	0.373	0.620	0.375											-5.839	Likely Benign	0.608	Likely Pathogenic	Likely Benign										0.192	Likely Benign	-0.82	Neutral	0.055	Benign	0.011	Benign	4.21	Benign	0.46	Tolerated			0.1335	0.4545		4	2	1.9	-18.03
c.520A>T	M174L 2D AIThe SynGAP1 missense variant M174L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Only AlphaMissense‑Default predicts a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Taken together, the majority of evidence points to a benign impact for M174L. This conclusion is consistent with the lack of ClinVar annotation and does not contradict any existing clinical classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.661982	Disordered	0.485854	Uncertain	0.373	0.620	0.375											-5.839	Likely Benign	0.608	Likely Pathogenic	Likely Benign										0.192	Likely Benign	-0.82	Neutral	0.055	Benign	0.011	Benign	4.21	Benign	0.46	Tolerated			0.1335	0.4545		4	2	1.9	-18.03
c.522G>A	M174I 2D AIThe SynGAP1 missense variant M174I is listed in gnomAD (ID 6‑33435164‑G‑A) but has no ClinVar record. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM; pathogenic predictions come from ESM1b and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as pathogenic, whereas the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 vs 2) and Foldetta results are unavailable. Overall, six tools predict benign while only two predict pathogenic, and the only high‑accuracy pathogenic call is from AlphaMissense‑Optimized. Thus, the variant is most likely benign based on the preponderance of evidence, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.661982	Disordered	0.485854	Uncertain	0.373	0.620	0.375								6-33435164-G-A	4	2.48e-6	-8.732	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic										0.120	Likely Benign	-1.63	Neutral	0.213	Benign	0.067	Benign	4.10	Benign	0.07	Tolerated	3.61	5	0.1191	0.3469		1	2	2.6	-18.03
c.522G>C	M174I 2D AIThe SynGAP1 missense variant M174I is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. Tools that predict a pathogenic effect are ESM1b and AlphaMissense‑Default. High‑accuracy methods give mixed results: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 pathogenic vs 2 benign), and Foldetta’s stability assessment is unavailable. Overall, the majority of standard predictors favor a benign outcome, and the high‑accuracy predictions do not override this trend. Thus, the variant is most likely benign, and this assessment does not contradict the lack of ClinVar reporting. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.661982	Disordered	0.485854	Uncertain	0.373	0.620	0.375											-8.732	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic										0.120	Likely Benign	-1.63	Neutral	0.213	Benign	0.067	Benign	4.10	Benign	0.07	Tolerated	3.61	5	0.1191	0.3469		1	2	2.6	-18.03
c.522G>T	M174I 2D AIThe SynGAP1 missense variant M174I is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. Tools that predict a pathogenic effect are ESM1b and AlphaMissense‑Default. High‑accuracy methods give mixed results: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 vs 2), and Foldetta data are unavailable. Overall, the majority of standard predictors indicate a benign impact, while the single high‑accuracy tool suggests pathogenicity but is not supported by consensus or folding‑stability evidence. Thus, the variant is most likely benign, and this assessment does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.661982	Disordered	0.485854	Uncertain	0.373	0.620	0.375											-8.732	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic										0.120	Likely Benign	-1.63	Neutral	0.213	Benign	0.067	Benign	4.10	Benign	0.07	Tolerated	3.61	5	0.1191	0.3469		1	2	2.6	-18.03
c.85A>C	M29L 2D AIThe SynGAP1 missense variant M29L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Based on the collective evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.541878	Disordered	0.438540	Uncertain	0.341	0.883	0.250											-1.633	Likely Benign	0.079	Likely Benign	Likely Benign										0.200	Likely Benign	-0.49	Neutral	0.006	Benign	0.039	Benign	4.27	Benign	0.00	Affected			0.1984	0.5336		4	2	1.9	-18.03
c.85A>T	M29L 2D AIThe SynGAP1 missense variant M29L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign effect; there is no conflict with ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.541878	Disordered	0.438540	Uncertain	0.341	0.883	0.250											-1.633	Likely Benign	0.079	Likely Benign	Likely Benign										0.200	Likely Benign	-0.49	Neutral	0.006	Benign	0.039	Benign	4.27	Benign	0.00	Affected			0.1984	0.5336		4	2	1.9	-18.03
c.865A>C	M289L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M289L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools largely agree on a benign effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as benign. Only FATHMM predicts a pathogenic outcome. Grouping by consensus, the benign‑predicting tools outnumber the single pathogenic prediction. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a “Likely Benign” verdict; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also reports a benign effect. No prediction or stability result is missing or inconclusive. Based on the collective evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.127496	Structured	0.403499	Uncertain	0.886	0.276	0.000											-5.778	Likely Benign	0.157	Likely Benign	Likely Benign	0.13	Likely Benign	0.0	-0.10	Likely Benign	0.02	Likely Benign	0.39	Likely Benign	0.070	Likely Benign	-0.95	Neutral	0.136	Benign	0.033	Benign	1.79	Pathogenic	0.27	Tolerated			0.1092	0.3634		4	2	1.9	-18.03
c.865A>T	M289L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M289L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only FATHMM predicts a pathogenic outcome. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign”; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is benign. No prediction or folding stability result is missing or inconclusive. Based on the collective evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar status because the variant is not currently listed in ClinVar. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.127496	Structured	0.403499	Uncertain	0.886	0.276	0.000											-5.778	Likely Benign	0.157	Likely Benign	Likely Benign	0.13	Likely Benign	0.0	-0.10	Likely Benign	0.02	Likely Benign	0.39	Likely Benign	0.070	Likely Benign	-0.95	Neutral	0.136	Benign	0.033	Benign	1.79	Pathogenic	0.27	Tolerated			0.1092	0.3634		4	2	1.9	-18.03
c.867G>A	M289I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M289I is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Optimized. Only FATHMM predicts a pathogenic outcome, while FoldX and AlphaMissense‑Default are uncertain. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a benign prediction; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts benign. Overall, the preponderance of evidence indicates that M289I is most likely benign, and this conclusion does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.127496	Structured	0.403499	Uncertain	0.886	0.276	0.000											-6.010	Likely Benign	0.505	Ambiguous	Likely Benign	0.62	Ambiguous	0.1	-0.23	Likely Benign	0.20	Likely Benign	0.36	Likely Benign	0.040	Likely Benign	-0.72	Neutral	0.005	Benign	0.018	Benign	1.78	Pathogenic	0.31	Tolerated			0.1001	0.2758		2	1	2.6	-18.03
c.867G>C	M289I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M289I is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Optimized. Only FATHMM predicts a pathogenic outcome, while FoldX and AlphaMissense‑Default are uncertain. High‑accuracy assessments reinforce the benign prediction: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a benign verdict; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts benign. Overall, the preponderance of evidence indicates that M289I is most likely benign, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.127496	Structured	0.403499	Uncertain	0.886	0.276	0.000											-6.010	Likely Benign	0.505	Ambiguous	Likely Benign	0.62	Ambiguous	0.1	-0.23	Likely Benign	0.20	Likely Benign	0.36	Likely Benign	0.040	Likely Benign	-0.72	Neutral	0.005	Benign	0.018	Benign	1.78	Pathogenic	0.31	Tolerated			0.1001	0.2758		2	1	2.6	-18.03
c.867G>T	M289I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M289I is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Optimized. Only FATHMM predicts a pathogenic outcome, while FoldX and AlphaMissense‑Default are uncertain. High‑accuracy assessments reinforce the benign prediction: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a benign verdict; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts benign. Overall, the preponderance of evidence indicates that M289I is most likely benign, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.127496	Structured	0.403499	Uncertain	0.886	0.276	0.000											-6.010	Likely Benign	0.505	Ambiguous	Likely Benign	0.62	Ambiguous	0.1	-0.23	Likely Benign	0.20	Likely Benign	0.36	Likely Benign	0.040	Likely Benign	-0.72	Neutral	0.005	Benign	0.018	Benign	1.78	Pathogenic	0.31	Tolerated			0.1001	0.2758		2	1	2.6	-18.03
c.87G>A	M29I 2D AIThe SynGAP1 missense variant M29I is catalogued in gnomAD (6-33423496‑G‑A) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all report benign or tolerated outcomes, while the single pathogenic signal comes from SIFT. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise indicates a benign likelihood. Foldetta stability analysis is unavailable for this variant. Overall, the preponderance of evidence points to a benign impact, and this conclusion is not contradicted by any ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.541878	Disordered	0.438540	Uncertain	0.341	0.883	0.250								6-33423496-G-A	6	3.72e-6	-2.425	Likely Benign	0.185	Likely Benign	Likely Benign										0.067	Likely Benign	-0.51	Neutral	0.006	Benign	0.091	Benign	4.26	Benign	0.00	Affected	4.32	1	0.1680	0.4385		1	2	2.6	-18.03
c.87G>C	M29I 2D AIThe SynGAP1 missense variant M29I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are not available. Based on the collective predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.541878	Disordered	0.438540	Uncertain	0.341	0.883	0.250											-2.425	Likely Benign	0.185	Likely Benign	Likely Benign										0.067	Likely Benign	-0.51	Neutral	0.006	Benign	0.091	Benign	4.26	Benign	0.00	Affected	4.32	1	0.1680	0.4385		1	2	2.6	-18.03
c.87G>T	M29I 2D AIThe SynGAP1 missense variant M29I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign effect, and this assessment does not contradict any ClinVar annotation (none is present). Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.541878	Disordered	0.438540	Uncertain	0.341	0.883	0.250											-2.425	Likely Benign	0.185	Likely Benign	Likely Benign										0.067	Likely Benign	-0.51	Neutral	0.006	Benign	0.091	Benign	4.26	Benign	0.00	Affected	4.32	1	0.1680	0.4385		1	2	2.6	-18.03
c.1189T>A	C397S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C397S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: REVEL, FoldX, premPS, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, PROVEAN, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign, while Rosetta remains uncertain. When predictions are grouped, the benign category contains all available evidence and the pathogenic category is empty. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign; the SGM Consensus (majority of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields benign; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, reports a benign effect. Consequently, the variant is most likely benign, and this conclusion is consistent with the absence of a ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.429200	Structured	0.395774	Uncertain	0.778	0.551	0.250											-2.324	Likely Benign	0.178	Likely Benign	Likely Benign	0.37	Likely Benign	0.1	0.59	Ambiguous	0.48	Likely Benign	0.43	Likely Benign	0.174	Likely Benign	-0.01	Neutral	0.276	Benign	0.066	Benign	4.68	Benign	0.53	Tolerated			0.5221	0.2474	Weaken	0	-1	-3.3	-16.06
c.1190G>C	C397S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C397S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). In silico prediction tools that assess pathogenicity largely agree on a benign outcome: REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. No tool predicts pathogenicity; Rosetta’s assessment is uncertain and therefore treated as unavailable. High‑accuracy methods reinforce this consensus: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is benign; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, is benign. Consequently, the variant is most likely benign based on the collective predictions, and this conclusion does not contradict any ClinVar status (none is assigned). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.429200	Structured	0.395774	Uncertain	0.778	0.551	0.250											-2.324	Likely Benign	0.178	Likely Benign	Likely Benign	0.37	Likely Benign	0.1	0.59	Ambiguous	0.48	Likely Benign	0.43	Likely Benign	0.253	Likely Benign	-0.01	Neutral	0.276	Benign	0.066	Benign	4.68	Benign	0.53	Tolerated			0.5221	0.2474	Weaken	0	-1	-3.3	-16.06
c.1294T>A	C432S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C432S is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM, whereas a majority of tools (SGM Consensus, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default) predict a pathogenic impact. Predictions that are inconclusive or unavailable are FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show SGM Consensus as likely pathogenic, AlphaMissense‑Optimized as uncertain, and Foldetta as uncertain. Overall, the balance of evidence favors a pathogenic classification for C432S, and this assessment does not contradict any ClinVar status because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.111485	Structured	0.362533	Uncertain	0.960	0.285	0.000											-8.229	Likely Pathogenic	0.913	Likely Pathogenic	Ambiguous	0.61	Ambiguous	0.1	0.96	Ambiguous	0.79	Ambiguous	1.52	Destabilizing	0.496	Likely Benign	-9.55	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.53	Benign	0.12	Tolerated			0.4262	0.1415		0	-1	-3.3	-16.06
c.1295G>C	C432S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C432S is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM, whereas a majority of tools (SGM Consensus, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default) predict a pathogenic impact. Predictions that are inconclusive or unavailable are FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show SGM Consensus as likely pathogenic, AlphaMissense‑Optimized as uncertain, and Foldetta as uncertain. Overall, the balance of evidence favors a pathogenic classification for C432S, and this assessment does not contradict any ClinVar status because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.111485	Structured	0.362533	Uncertain	0.960	0.285	0.000											-8.229	Likely Pathogenic	0.913	Likely Pathogenic	Ambiguous	0.61	Ambiguous	0.1	0.96	Ambiguous	0.79	Ambiguous	1.52	Destabilizing	0.417	Likely Benign	-9.55	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.53	Benign	0.12	Tolerated			0.4262	0.1415		0	-1	-3.3	-16.06
c.145T>A	C49S 2D AIThe SynGAP1 missense variant C49S is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs. 2 pathogenic votes). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of standard predictors lean toward pathogenicity, but the high‑accuracy tools do not provide definitive support. Thus, the variant is most likely pathogenic based on the current predictions, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.209395	Structured	0.445316	Uncertain	0.541	0.704	0.000											-6.575	Likely Benign	0.704	Likely Pathogenic	Likely Benign										0.260	Likely Benign	-3.07	Deleterious	0.462	Possibly Damaging	0.478	Possibly Damaging	3.91	Benign	0.00	Affected			0.3855	0.1686		0	-1	-3.3	-16.06
c.146G>C	C49S 2D AIThe SynGAP1 missense variant C49S is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic). Foldetta results are unavailable. Overall, the majority of conventional tools (five pathogenic vs four benign) lean toward a pathogenic interpretation, but the single high‑accuracy benign prediction and the inconclusive SGM Consensus leave the assessment uncertain. Thus, the variant is most likely pathogenic based on the prevailing predictions, and this does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.209395	Structured	0.445316	Uncertain	0.541	0.704	0.000											-6.575	Likely Benign	0.704	Likely Pathogenic	Likely Benign										0.224	Likely Benign	-3.07	Deleterious	0.462	Possibly Damaging	0.478	Possibly Damaging	3.91	Benign	0.00	Affected			0.3855	0.1686		0	-1	-3.3	-16.06
c.1570T>A	C524S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C524S is listed in gnomAD (variant ID 6‑33438813‑T‑A) but has no ClinVar entry. Prediction tools that assess pathogenicity all converge on a deleterious effect: REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all report a pathogenic outcome, while FoldX, Rosetta, and Foldetta are uncertain and therefore not counted as evidence. Grouping by agreement yields a benign‑prediction set that is empty and a pathogenic‑prediction set that contains the eleven tools above. High‑accuracy assessments reinforce this: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic; Foldetta remains uncertain. Consequently, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.134866	Structured	0.024729	Uncertain	0.916	0.385	0.125								6-33438813-T-A	1	6.20e-7	-11.174	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	0.80	Ambiguous	0.1	1.55	Ambiguous	1.18	Ambiguous	1.58	Destabilizing	0.915	Likely Pathogenic	-9.94	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.38	Pathogenic	0.00	Affected	3.37	35	0.5362	0.1848	Weaken	-1	0	-3.3	-16.06
c.1571G>C	C524S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 C524S variant has no ClinVar entry and is not present in gnomAD. Prediction tools that agree on a benign effect are none; those that predict pathogenicity include REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX, Rosetta, and Foldetta returned inconclusive results and are treated as unavailable evidence. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta as inconclusive. Overall, the preponderance of evidence points to a pathogenic effect. This conclusion is not contradicted by ClinVar status, which simply lacks an entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.134866	Structured	0.024729	Uncertain	0.916	0.385	0.125											-11.174	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	0.80	Ambiguous	0.1	1.55	Ambiguous	1.18	Ambiguous	1.58	Destabilizing	0.904	Likely Pathogenic	-9.94	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.38	Pathogenic	0.00	Affected	3.37	35	0.5362	0.1848	Weaken	-1	0	-3.3	-16.06
c.1591T>A	C531S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C531S is not reported in ClinVar and has no entries in gnomAD. Prediction tools that assess pathogenicity largely agree on a deleterious effect: SGM‑Consensus, REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default all predict pathogenic. In contrast, only three tools predict a benign outcome: FoldX, Foldetta, and AlphaMissense‑Optimized. High‑accuracy methods provide a mixed picture: AlphaMissense‑Optimized reports a benign effect, the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic, and Foldetta also predicts benign stability. Overall, the preponderance of evidence points to a pathogenic impact for C531S. This conclusion is not contradicted by ClinVar, which contains no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.281712	Structured	0.017941	Uncertain	0.878	0.401	0.000											-8.213	Likely Pathogenic	0.575	Likely Pathogenic	Likely Benign	-0.02	Likely Benign	0.0	0.77	Ambiguous	0.38	Likely Benign	1.23	Destabilizing	0.519	Likely Pathogenic	-8.00	Deleterious	0.958	Probably Damaging	0.533	Possibly Damaging	-1.18	Pathogenic	0.01	Affected			0.3716	0.1782		0	-1	-3.3	-16.06
c.1592G>C	C531S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C531S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from FoldX, Foldetta, and AlphaMissense‑Optimized, whereas pathogenic predictions are made by SGM‑Consensus, REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default; Rosetta remains uncertain. High‑accuracy assessments further support a pathogenic bias: AlphaMissense‑Optimized indicates benign, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—classifies the variant as pathogenic, and Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, predicts benign. Overall, the preponderance of evidence points to a pathogenic effect for C531S, and this conclusion does not conflict with the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.281712	Structured	0.017941	Uncertain	0.878	0.401	0.000											-8.213	Likely Pathogenic	0.575	Likely Pathogenic	Likely Benign	-0.02	Likely Benign	0.0	0.77	Ambiguous	0.38	Likely Benign	1.23	Destabilizing	0.508	Likely Pathogenic	-8.00	Deleterious	0.958	Probably Damaging	0.533	Possibly Damaging	-1.18	Pathogenic	0.01	Affected			0.3716	0.1782		0	-1	-3.3	-16.06
c.1636T>A	C546S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C546S is reported in gnomAD (ID 6‑33438879‑T‑A) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions from FoldX and SIFT; pathogenic predictions from REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Two tools give uncertain results: Rosetta and Foldetta. High‑accuracy assessments reinforce a pathogenic signal: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels the variant as Likely Pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta outputs, remains inconclusive. Overall, the preponderance of evidence, including the high‑accuracy tools, indicates that C546S is most likely pathogenic, and this assessment does not conflict with any ClinVar classification because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.027463	Structured	0.009041	Uncertain	0.960	0.288	0.000								6-33438879-T-A	1	6.20e-7	-8.079	Likely Pathogenic	0.988	Likely Pathogenic	Likely Pathogenic	0.44	Likely Benign	0.1	1.39	Ambiguous	0.92	Ambiguous	1.65	Destabilizing	0.836	Likely Pathogenic	-8.04	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.21	Pathogenic	0.17	Tolerated	3.37	35	0.4343	0.1950		-1	0	-3.3	-16.06
c.1637G>C	C546S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C546S is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include FoldX and SIFT, whereas the majority of tools predict a pathogenic impact: REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Rosetta and Foldetta are uncertain, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM Consensus as likely pathogenic, and Foldetta as uncertain. Overall, the preponderance of evidence points to a pathogenic effect for C546S, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.027463	Structured	0.009041	Uncertain	0.960	0.288	0.000											-8.079	Likely Pathogenic	0.988	Likely Pathogenic	Likely Pathogenic	0.44	Likely Benign	0.1	1.39	Ambiguous	0.92	Ambiguous	1.65	Destabilizing	0.788	Likely Pathogenic	-8.04	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.21	Pathogenic	0.17	Tolerated	3.37	35	0.4343	0.1950		-1	0	-3.3	-16.06
c.1639T>A	C547S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C547S is not reported in ClinVar (ClinVar status: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a pathogenic effect include SGM‑Consensus, REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. No tools predict a benign outcome. Predictions that are uncertain or inconclusive are FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the preponderance of evidence points to a pathogenic effect. This conclusion is consistent with the lack of ClinVar annotation and does not contradict any existing database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.045352	Structured	0.007912	Uncertain	0.971	0.275	0.000											-11.888	Likely Pathogenic	0.946	Likely Pathogenic	Ambiguous	0.85	Ambiguous	0.0	1.73	Ambiguous	1.29	Ambiguous	1.76	Destabilizing	0.884	Likely Pathogenic	-9.64	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.27	Pathogenic	0.04	Affected			0.4542	0.1792		0	-1	-3.3	-16.06
c.1640G>C	C547S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C547S is not reported in ClinVar (ClinVar status: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a pathogenic effect include SGM‑Consensus, REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. No tools predict a benign outcome. Predictions that are uncertain or inconclusive are FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the preponderance of evidence points to a pathogenic effect. This conclusion is consistent with the lack of ClinVar annotation and does not contradict any existing database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.045352	Structured	0.007912	Uncertain	0.971	0.275	0.000											-11.888	Likely Pathogenic	0.946	Likely Pathogenic	Ambiguous	0.85	Ambiguous	0.0	1.73	Ambiguous	1.29	Ambiguous	1.76	Destabilizing	0.825	Likely Pathogenic	-9.64	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.27	Pathogenic	0.04	Affected			0.4542	0.1792		0	-1	-3.3	-16.06
c.1654T>A	C552S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C552S is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include FoldX, Rosetta, Foldetta, and SIFT, whereas a majority of tools predict a pathogenic impact: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic). The high‑accuracy assessments are mixed: AlphaMissense‑Optimized classifies the variant as pathogenic, the SGM‑Consensus also indicates a likely pathogenic outcome, whereas Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, reports a benign effect. premPS is inconclusive. Overall, the preponderance of evidence from multiple independent predictors points to a pathogenic effect for C552S. This conclusion is not contradicted by ClinVar status, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.013265	Structured	0.005714	Uncertain	0.955	0.256	0.000											-9.309	Likely Pathogenic	0.985	Likely Pathogenic	Likely Pathogenic	-0.27	Likely Benign	0.0	-0.34	Likely Benign	-0.31	Likely Benign	0.97	Ambiguous	0.748	Likely Pathogenic	-8.21	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.15	Pathogenic	0.69	Tolerated			0.3469	0.1415		0	-1	-3.3	-16.06
c.1655G>C	C552S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C552S is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include FoldX, Rosetta, Foldetta, and SIFT, whereas a majority of tools predict a pathogenic impact: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic). The high‑accuracy assessments are mixed: AlphaMissense‑Optimized classifies the variant as pathogenic, the SGM‑Consensus also indicates a likely pathogenic outcome, whereas Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, reports a benign effect. premPS is inconclusive. Overall, the preponderance of evidence from multiple independent predictors points to a pathogenic effect for C552S. This conclusion is not contradicted by ClinVar status, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.013265	Structured	0.005714	Uncertain	0.955	0.256	0.000											-9.309	Likely Pathogenic	0.985	Likely Pathogenic	Likely Pathogenic	-0.27	Likely Benign	0.0	-0.34	Likely Benign	-0.31	Likely Benign	0.97	Ambiguous	0.684	Likely Pathogenic	-8.21	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.15	Pathogenic	0.69	Tolerated			0.3469	0.1415		0	-1	-3.3	-16.06
c.1675T>A	C559S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C559S is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, SIFT, and FATHMM. Tools that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. The remaining tools, premPS and AlphaMissense‑Optimized, are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) as Benign. Based on the overall distribution of predictions, the variant is most likely pathogenic; this conclusion does not contradict the ClinVar status, which has no classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.016021	Structured	0.010460	Uncertain	0.842	0.204	0.000											-10.756	Likely Pathogenic	0.785	Likely Pathogenic	Ambiguous	-0.03	Likely Benign	0.0	-0.31	Likely Benign	-0.17	Likely Benign	0.65	Ambiguous	0.450	Likely Benign	-7.26	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.58	Benign	0.64	Tolerated			0.3940	0.1319		0	-1	-3.3	-16.06
c.1676G>C	C559S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C559S has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, SIFT, and FATHMM. Those that predict a pathogenic impact are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Two tools give inconclusive results: premPS (Uncertain) and AlphaMissense‑Optimized (Uncertain). High‑accuracy assessments show SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, Foldetta (combining FoldX‑MD and Rosetta) as Benign, and AlphaMissense‑Optimized as Uncertain. Overall, the majority of predictions lean toward pathogenicity, and this conclusion does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.016021	Structured	0.010460	Uncertain	0.842	0.204	0.000											-10.756	Likely Pathogenic	0.785	Likely Pathogenic	Ambiguous	-0.03	Likely Benign	0.0	-0.31	Likely Benign	-0.17	Likely Benign	0.65	Ambiguous	0.469	Likely Benign	-7.26	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.58	Benign	0.64	Tolerated			0.3940	0.1319		0	-1	-3.3	-16.06
c.1726T>A	C576S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C576S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign predictions from REVEL and FATHMM, while the majority of other in silico methods (premPS, PROVEAN, polyPhen‑2 HumDiv/HumVar, SIFT, ESM1b, AlphaMissense‑Default) predict pathogenicity. FoldX and Rosetta give uncertain stability changes, and Foldetta likewise reports no definitive effect. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenic, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic. Foldetta remains inconclusive. Overall, the preponderance of evidence from multiple pathogenic‑oriented tools and the high‑accuracy predictions indicates that C576S is most likely pathogenic, which is consistent with the absence of a ClinVar entry and gnomAD data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.113710	Structured	0.017684	Uncertain	0.913	0.245	0.000											-10.474	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	0.77	Ambiguous	0.1	1.57	Ambiguous	1.17	Ambiguous	1.61	Destabilizing	0.414	Likely Benign	-8.91	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.40	Benign	0.02	Affected			0.4968	0.1464		0	-1	-3.3	-16.06
c.1727G>C	C576S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C576S is not reported in ClinVar and has no entries in gnomAD. Prediction tools that indicate a benign effect are limited to FATHMM, whereas the remaining 11 tools (SGM‑Consensus, REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) all predict a pathogenic or likely pathogenic outcome. High‑accuracy methods reinforce this trend: AlphaMissense‑Optimized reports pathogenic; the SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also returns likely pathogenic; Foldetta, a protein‑folding stability predictor combining FoldX‑MD and Rosetta, is inconclusive. Folding‑stability tools FoldX and Rosetta individually yield uncertain results and are treated as unavailable. Taken together, the majority of evidence points to a pathogenic effect. This conclusion is consistent with the absence of ClinVar annotation and gnomAD data, so there is no contradiction with existing database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.113710	Structured	0.017684	Uncertain	0.913	0.245	0.000											-10.474	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	0.77	Ambiguous	0.1	1.57	Ambiguous	1.17	Ambiguous	1.61	Destabilizing	0.523	Likely Pathogenic	-8.91	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.40	Benign	0.02	Affected			0.4968	0.1464		0	-1	-3.3	-16.06
c.1795T>A	C599S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C599S is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only SIFT, which scores the variant as benign. All other evaluated algorithms—REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and the SGM Consensus—predict a pathogenic or likely pathogenic outcome. High‑accuracy assessments show the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Pathogenic, AlphaMissense‑Optimized as Uncertain, and Foldetta (combining FoldX‑MD and Rosetta) as Uncertain. No prediction or folding stability result is missing; all available data are reported. Based on the preponderance of pathogenic predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.009865	Structured	0.151725	Uncertain	0.960	0.151	0.000											-13.336	Likely Pathogenic	0.954	Likely Pathogenic	Ambiguous	0.85	Ambiguous	0.0	1.57	Ambiguous	1.21	Ambiguous	1.27	Destabilizing	0.919	Likely Pathogenic	-9.95	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.45	Pathogenic	0.06	Tolerated			0.3414	0.1415		0	-1	-3.3	-16.06
c.1796G>C	C599S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C599S is not reported in ClinVar and has no entries in gnomAD. Prediction tools cluster into two groups: the sole benign prediction comes from SIFT, whereas the remaining nine tools—REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus—indicate pathogenicity. High‑accuracy assessments give a mixed picture: AlphaMissense‑Optimized is uncertain, SGM‑Consensus predicts likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is uncertain. FoldX and Rosetta individually report uncertain stability changes. Overall, the majority of evidence points to a deleterious effect, so the variant is most likely pathogenic, with no ClinVar annotation to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.009865	Structured	0.151725	Uncertain	0.960	0.151	0.000											-13.336	Likely Pathogenic	0.954	Likely Pathogenic	Ambiguous	0.85	Ambiguous	0.0	1.57	Ambiguous	1.21	Ambiguous	1.27	Destabilizing	0.866	Likely Pathogenic	-9.95	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.45	Pathogenic	0.06	Tolerated			0.3414	0.1415		0	-1	-3.3	-16.06
c.2461T>A	C821S 2D AIThe SynGAP1 missense variant C821S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, whereas the SGM‑Consensus (majority vote) supports a benign outcome. Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for C821S, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.745909	Disordered	0.672821	Binding	0.351	0.883	0.750											-0.425	Likely Benign	0.898	Likely Pathogenic	Ambiguous										0.190	Likely Benign	-0.47	Neutral	0.997	Probably Damaging	0.994	Probably Damaging	2.91	Benign	1.00	Tolerated			0.5284	0.2012	Weaken	0	-1	-3.3	-16.06
c.2462G>C	C821S 2D AIThe SynGAP1 missense variant C821S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, whereas the SGM‑Consensus (majority vote) supports a benign outcome. Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for C821S, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.745909	Disordered	0.672821	Binding	0.351	0.883	0.750											-0.425	Likely Benign	0.898	Likely Pathogenic	Ambiguous										0.314	Likely Benign	-0.47	Neutral	0.997	Probably Damaging	0.994	Probably Damaging	2.91	Benign	1.00	Tolerated			0.5284	0.2012	Weaken	0	-1	-3.3	-16.06
c.655T>A	C219S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C219S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: benign calls come from FoldX, polyPhen‑2 HumVar, and FATHMM, while pathogenic predictions are made by SGM‑Consensus (Likely Pathogenic), REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments reinforce this trend: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates pathogenicity, and Foldetta, which integrates FoldX‑MD and Rosetta outputs, is inconclusive. With the majority of evidence pointing to a damaging effect and no ClinVar annotation to contradict, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.254060	Structured	0.426845	Uncertain	0.903	0.279	0.000											-12.962	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	0.09	Likely Benign	0.4	1.53	Ambiguous	0.81	Ambiguous	1.56	Destabilizing	0.892	Likely Pathogenic	-8.35	Deleterious	0.900	Possibly Damaging	0.380	Benign	5.95	Benign	0.04	Affected			0.3568	0.1454		0	-1	-3.3	-16.06
c.656G>C	C219S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C219S is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include FoldX, polyPhen‑2 HumVar, and FATHMM, whereas the majority of tools predict it to be pathogenic: SGM‑Consensus, REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates pathogenicity, and Foldetta’s stability analysis is inconclusive (treated as unavailable). Taken together, the preponderance of evidence from both general and high‑accuracy predictors points to a pathogenic impact for C219S. This conclusion is not contradicted by ClinVar status, which has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.254060	Structured	0.426845	Uncertain	0.903	0.279	0.000											-12.962	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	0.09	Likely Benign	0.4	1.53	Ambiguous	0.81	Ambiguous	1.56	Destabilizing	0.817	Likely Pathogenic	-8.35	Deleterious	0.900	Possibly Damaging	0.380	Benign	5.95	Benign	0.04	Affected			0.3568	0.1454		0	-1	-3.3	-16.06
c.688T>A	C230S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C230S is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include FoldX, Rosetta, Foldetta, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. Those that predict a pathogenic effect are REVEL, premPS, PROVEAN, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as likely pathogenic, and Foldetta as benign. With an equal split of 7 benign versus 7 pathogenic predictions overall, the higher‑confidence tools lean toward pathogenicity. Therefore, the variant is most likely pathogenic based on the available predictions, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.268042	Structured	0.308076	Uncertain	0.870	0.308	0.000											-9.994	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	0.42	Likely Benign	0.1	0.05	Likely Benign	0.24	Likely Benign	1.08	Destabilizing	0.859	Likely Pathogenic	-8.24	Deleterious	0.421	Benign	0.115	Benign	5.91	Benign	0.07	Tolerated			0.4926	0.1822		0	-1	-3.3	-16.06
c.689G>C	C230S 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant C230S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools cluster into two groups: benign calls come from FoldX, Rosetta, Foldetta, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM; pathogenic calls come from REVEL, premPS, PROVEAN, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic, and Foldetta as benign. No prediction or stability result is missing. Overall, the predictions are evenly split between benign and pathogenic, leaving the variant’s functional impact uncertain. This uncertainty does not contradict ClinVar status, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.268042	Structured	0.308076	Uncertain	0.870	0.308	0.000											-9.994	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	0.42	Likely Benign	0.1	0.05	Likely Benign	0.24	Likely Benign	1.08	Destabilizing	0.844	Likely Pathogenic	-8.24	Deleterious	0.421	Benign	0.115	Benign	5.91	Benign	0.07	Tolerated			0.4926	0.1822		0	-1	-3.3	-16.06
c.697T>A	C233S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C233S is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Those that predict a pathogenic effect are REVEL, premPS, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX, Rosetta, and Foldetta give uncertain results and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also favors pathogenicity (3 pathogenic vs 1 benign). Foldetta remains uncertain. Overall, the majority of evidence points to a pathogenic impact. This conclusion does not contradict ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.239899	Structured	0.306787	Uncertain	0.868	0.322	0.000											-10.862	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic	0.61	Ambiguous	0.1	1.25	Ambiguous	0.93	Ambiguous	1.50	Destabilizing	0.764	Likely Pathogenic	-8.89	Deleterious	0.421	Benign	0.080	Benign	5.79	Benign	0.03	Affected			0.4528	0.2833		0	-1	-3.3	-16.06
c.698G>C	C233S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C233S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM, while pathogenic predictions arise from SGM‑Consensus, REVEL, premPS, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Pathogenic.” Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, yields an uncertain result and is treated as unavailable evidence. Overall, the preponderance of evidence points to a pathogenic impact for C233S, and this conclusion does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.239899	Structured	0.306787	Uncertain	0.868	0.322	0.000											-10.862	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic	0.61	Ambiguous	0.1	1.25	Ambiguous	0.93	Ambiguous	1.50	Destabilizing	0.830	Likely Pathogenic	-8.89	Deleterious	0.421	Benign	0.080	Benign	5.79	Benign	0.03	Affected			0.4528	0.2833		0	-1	-3.3	-16.06
c.844T>A	C282S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C282S is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that indicate a benign effect include REVEL, whereas the majority of other in‑silico predictors (premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) all classify the variant as pathogenic. Stability‑based methods (FoldX, Rosetta, and Foldetta) return uncertain results and are therefore not considered evidence for or against pathogenicity. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as Likely Pathogenic, and Foldetta as uncertain. Based on the preponderance of pathogenic predictions, the variant is most likely pathogenic, which does not contradict its current ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.098513	Structured	0.348535	Uncertain	0.942	0.250	0.000					Uncertain		1				-11.846	Likely Pathogenic	0.958	Likely Pathogenic	Likely Pathogenic	1.55	Ambiguous	0.1	1.23	Ambiguous	1.39	Ambiguous	1.62	Destabilizing	0.460	Likely Benign	-9.19	Deleterious	0.997	Probably Damaging	0.994	Probably Damaging	1.64	Pathogenic	0.03	Affected	3.39	18	0.5009	0.1286	Weaken	0	-1	-3.3	-16.06	233.2	14.8	-0.1	0.0	-0.2	0.3						X		Potentially Benign	The thiol-containing side chain of Cys282, located at the beginning of an anti-parallel β sheet strand (res. Arg279-Leu286), packs against multiple hydrophobic residues (e.g., Ile268, Leu284, Trp308, Leu327). In the variant simulations, the hydroxyl-containing side chain of Ser282 is more hydrophilic and, hence, not as favorable as Cys282 for this hydrophobic niche. Due to this polarity difference, the residue swap could potentially weaken the hydrophobic packing of the C2 domain during the folding process.Moreover, because the C2 domain interacts with the membrane, there could also be a negative effect on the stability of the SynGAP-membrane association. However, no large-scale structural changes were observed during the variant simulations. The hydroxyl group of Ser282 forms a hydrogen bond with the backbone carbonyl group of His326 in another β strand (res. Ala322-Arg329), which competes directly with the backbone amide group of Glu283 within the secondary structure element.
c.845G>C	C282S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C282S is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated algorithms predict a pathogenic impact: premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Predictions from FoldX, Rosetta, and Foldetta are inconclusive and are treated as unavailable. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus is likely pathogenic, while Foldetta remains uncertain. Based on the preponderance of pathogenic predictions and the lack of benign evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.098513	Structured	0.348535	Uncertain	0.942	0.250	0.000											-11.846	Likely Pathogenic	0.958	Likely Pathogenic	Likely Pathogenic	1.55	Ambiguous	0.1	1.23	Ambiguous	1.39	Ambiguous	1.62	Destabilizing	0.436	Likely Benign	-9.19	Deleterious	0.997	Probably Damaging	0.994	Probably Damaging	1.64	Pathogenic	0.03	Affected	3.39	18	0.5009	0.1286	Weaken	0	-1	-3.3	-16.06	233.2	14.8	-0.1	0.0	-0.2	0.3						X		Potentially Benign	The thiol-containing side chain of Cys282, located at the beginning of an anti-parallel β sheet strand (res. Arg279-Leu286), packs against multiple hydrophobic residues (e.g., Ile268, Leu284, Trp308, Leu327). In the variant simulations, the hydroxyl-containing side chain of Ser282 is more hydrophilic and, hence, not as favorable as Cys282 for this hydrophobic niche. Due to this polarity difference, the residue swap could potentially weaken the hydrophobic packing of the C2 domain during the folding process.Moreover, because the C2 domain interacts with the membrane, there could also be a negative effect on the stability of the SynGAP-membrane association. However, no large-scale structural changes were observed during the variant simulations. The hydroxyl group of Ser282 forms a hydrogen bond with the backbone carbonyl group of His326 in another β strand (res. Ala322-Arg329), which competes directly with the backbone amide group of Glu283 within the secondary structure element.
c.853T>A	C285S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C285S has no ClinVar record and is not reported in gnomAD. Prediction tools that agree on a benign effect include only SIFT, whereas a majority of the remaining predictors (REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, AlphaMissense‑Default) indicate a pathogenic impact. The remaining tools (FoldX, Rosetta, Foldetta, ESM1b, AlphaMissense‑Optimized) return uncertain results, which are treated as unavailable evidence. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta as uncertain. Overall, the preponderance of evidence points to a pathogenic effect, and this conclusion does not contradict any ClinVar status (none). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.144935	Structured	0.375400	Uncertain	0.946	0.250	0.000											-7.149	In-Between	0.868	Likely Pathogenic	Ambiguous	0.73	Ambiguous	0.1	0.75	Ambiguous	0.74	Ambiguous	1.20	Destabilizing	0.507	Likely Pathogenic	-8.09	Deleterious	0.997	Probably Damaging	0.994	Probably Damaging	1.90	Pathogenic	0.08	Tolerated			0.5210	0.2038	Weaken	0	-1	-3.3	-16.06
c.854G>C	C285S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C285S is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL and SIFT, whereas premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Default all predict a pathogenic outcome. Predictions from FoldX, Rosetta, ESM1b, AlphaMissense‑Optimized, and Foldetta are inconclusive. High‑accuracy methods give the following results: AlphaMissense‑Optimized is uncertain; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely pathogenic classification; Foldetta, which integrates FoldX‑MD and Rosetta outputs, is also uncertain. Overall, the preponderance of evidence points to a pathogenic effect for C285S, and this assessment does not conflict with the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.144935	Structured	0.375400	Uncertain	0.946	0.250	0.000											-7.149	In-Between	0.868	Likely Pathogenic	Ambiguous	0.73	Ambiguous	0.1	0.75	Ambiguous	0.74	Ambiguous	1.20	Destabilizing	0.499	Likely Benign	-8.09	Deleterious	0.997	Probably Damaging	0.994	Probably Damaging	1.90	Pathogenic	0.08	Tolerated			0.5210	0.2038	Weaken	0	-1	-3.3	-16.06
c.1034T>C	L345P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L345P is not reported in ClinVar (ClinVar status: not listed) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated algorithms—FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus (majority vote) is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. Based on the collective predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.260850	Structured	0.354989	Uncertain	0.936	0.478	0.125											-10.994	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	3.33	Destabilizing	0.2	3.26	Destabilizing	3.30	Destabilizing	1.27	Destabilizing	0.335	Likely Benign	-4.80	Deleterious	0.998	Probably Damaging	0.889	Possibly Damaging	1.70	Pathogenic	0.02	Affected			0.3581	0.1342		-3	-3	-5.4	-16.04
c.1058T>C	L353P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L353P is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Functional prediction tools show a strong bias toward pathogenicity: REVEL predicts benign, whereas FoldX, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default all predict pathogenic. Two tools report uncertainty: ESM1b and AlphaMissense‑Optimized. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is inconclusive, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenic. Overall, the majority of evidence points to a pathogenic impact, which is consistent with the ClinVar designation of uncertain significance but leans toward pathogenicity rather than benign. Thus, the variant is most likely pathogenic, and this prediction does not contradict the ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.137348	Structured	0.373584	Uncertain	0.926	0.315	0.000					Uncertain		1				-7.913	In-Between	0.936	Likely Pathogenic	Ambiguous	4.63	Destabilizing	0.1	10.19	Destabilizing	7.41	Destabilizing	2.17	Destabilizing	0.464	Likely Benign	-3.70	Deleterious	0.947	Possibly Damaging	0.454	Possibly Damaging	1.29	Pathogenic	0.02	Affected	3.37	25	0.3582	0.1645		-3	-3	-5.4	-16.04
c.1100T>C	L367P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L367P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Functional prediction tools that agree on benign impact include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote). Tools that predict pathogenicity are FoldX, Rosetta, Foldetta, polyPhen‑2 HumDiv, SIFT, and FATHMM; premPS remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus as likely benign, while Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a pathogenic effect. Overall, the majority of predictions lean toward a benign effect, and this conclusion does not contradict any ClinVar annotation because no ClinVar status exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.370445	Structured	0.441805	Uncertain	0.790	0.657	0.250											-2.418	Likely Benign	0.160	Likely Benign	Likely Benign	2.13	Destabilizing	0.4	4.05	Destabilizing	3.09	Destabilizing	0.72	Ambiguous	0.212	Likely Benign	-0.50	Neutral	0.627	Possibly Damaging	0.196	Benign	1.72	Pathogenic	0.02	Affected			0.3946	0.1874		-3	-3	-5.4	-16.04
c.1205T>C	L402P 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L402P is not reported in ClinVar and is absent from gnomAD. Consensus among in‑silico predictors is overwhelmingly pathogenic: SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a deleterious effect, whereas only FATHMM predicts a benign outcome. High‑accuracy tools reinforce this view: AlphaMissense‑Optimized scores the variant as pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely pathogenic effect; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts pathogenicity. Taken together, the evidence strongly supports a pathogenic classification, and this assessment does not conflict with the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.243554	Structured	0.431978	Uncertain	0.961	0.383	0.000											-12.030	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	7.40	Destabilizing	0.1	5.82	Destabilizing	6.61	Destabilizing	2.22	Destabilizing	0.616	Likely Pathogenic	-4.80	Deleterious	1.000	Probably Damaging	0.980	Probably Damaging	3.68	Benign	0.01	Affected			0.3628	0.1874		-3	-3	-5.4	-16.04
c.1247T>C	L416P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L416P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign predictions from REVEL, SIFT, and FATHMM; pathogenic predictions from the remaining 13 tools (FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen2_HumDiv, polyPhen2_HumVar, AlphaMissense‑Default, AlphaMissense‑Optimized, ESM1b, and the SGM Consensus). High‑accuracy methods specifically indicate pathogenicity: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. No predictions are inconclusive. Based on the overall consensus of the majority of tools and the high‑accuracy methods, the variant is most likely pathogenic, which is consistent with the lack of ClinVar reporting and gnomAD absence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.104810	Structured	0.336105	Uncertain	0.935	0.227	0.000											-8.859	Likely Pathogenic	0.975	Likely Pathogenic	Likely Pathogenic	2.59	Destabilizing	0.1	6.23	Destabilizing	4.41	Destabilizing	1.27	Destabilizing	0.284	Likely Benign	-3.56	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.35	Benign	0.21	Tolerated			0.3589	0.1353		-3	-3	-5.4	-16.04
c.1292T>C	L431P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L431P (ClinVar ID 661045.0) is reported as Pathogenic and is not present in gnomAD. Prediction tools that classify the variant as benign include only FATHMM. All other evaluated tools—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict it to be pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts Pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts Pathogenic. Based on the overwhelming consensus of pathogenic predictions and the ClinVar designation, the variant is most likely pathogenic, with no contradiction to its ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.094817	Structured	0.374755	Uncertain	0.959	0.300	0.000					Likely Pathogenic		1				-14.222	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	6.78	Destabilizing	0.3	11.59	Destabilizing	9.19	Destabilizing	2.29	Destabilizing	0.659	Likely Pathogenic	-6.39	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.91	Benign	0.05	Affected	3.37	29	0.3484	0.2163		-3	-3	-5.4	-16.04	222.4	62.8	0.1	0.0	0.1	0.0	X							Potentially Pathogenic	The iso-butyl side chain of Leu431, located in an α helix (res. Met414-Glu436), packs against other hydrophobic residues in an interhelix space (e.g., Val434, Leu435, Leu696, Leu711) in the WT simulations. While the backbone amide group of Leu431 forms an H-bond with the carbonyl group of His427, the cyclic five-membered pyrrolidine ring of Pro431, lacking the necessary amide group, cannot do the same. Thus, although the cyclic five-membered pyrrolidine ring of Pro431 packs almost as favorably as the side chain of Leu431 in the hydrophobic niche, the residue swap causes the α helix to partially unfold in the variant simulations.
c.1316T>C	L439P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L439P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools largely agree on a deleterious effect: pathogenic predictions come from SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only FATHMM predicts a benign outcome. High‑accuracy methods reinforce the pathogenic view: AlphaMissense‑Optimized is pathogenic, SGM‑Consensus is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. No predictions are missing or inconclusive. Based on the overwhelming consensus of pathogenic predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.222385	Structured	0.281542	Uncertain	0.942	0.265	0.000											-9.929	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	6.30	Destabilizing	0.2	7.62	Destabilizing	6.96	Destabilizing	1.28	Destabilizing	0.539	Likely Pathogenic	-5.72	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.21	Benign	0.02	Affected			0.3426	0.1192		-3	-3	-5.4	-16.04
c.1352T>C	L451P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L451P is reported in ClinVar as Pathogenic (ClinVar ID 3064222.0) and is not found in gnomAD. Prediction tools that assess functional impact uniformly classify the variant as pathogenic: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign effect. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. Based on these predictions, the variant is most likely pathogenic, and this conclusion aligns with its ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.281712	Structured	0.314017	Uncertain	0.978	0.232	0.000					Likely Pathogenic		1				-14.549	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	6.92	Destabilizing	0.2	8.57	Destabilizing	7.75	Destabilizing	2.58	Destabilizing	0.750	Likely Pathogenic	-6.81	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	2.43	Pathogenic	0.00	Affected	3.37	34	0.2823	0.1221		-3	-3	-5.4	-16.04
c.1364T>C	L455P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L455P is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include only FATHMM, whereas all other evaluated algorithms—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support this: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, is pathogenic. No predictions are missing or inconclusive. Based on the overwhelming agreement among these tools, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.188120	Structured	0.310377	Uncertain	0.963	0.168	0.000											-14.150	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	7.45	Destabilizing	0.2	11.99	Destabilizing	9.72	Destabilizing	2.19	Destabilizing	0.695	Likely Pathogenic	-6.72	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.23	Benign	0.00	Affected			0.3211	0.1221		-3	-3	-5.4	-16.04
c.1394T>C	L465P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L465P is listed in ClinVar as Pathogenic (ClinVar ID 1067821.0) and is not reported in gnomAD. Prediction tools that assess functional impact uniformly classify the variant as pathogenic: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign effect. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenicity. Based on the unanimous computational evidence, the variant is most likely pathogenic, and this conclusion aligns with its ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.346032	Structured	0.319240	Uncertain	0.956	0.202	0.000					Likely Pathogenic		1				-14.824	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	7.18	Destabilizing	0.3	10.85	Destabilizing	9.02	Destabilizing	2.73	Destabilizing	0.778	Likely Pathogenic	-6.96	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	2.29	Pathogenic	0.00	Affected	3.37	34	0.3387	0.1582		-3	-3	-5.4	-16.04	211.1	65.9	0.1	0.0	-0.2	0.0	X							Potentially Pathogenic	The iso-butyl side chain of Leu465, located in the middle of an α helix (res. Ala461–Phe476), packs with hydrophobic residues (e.g., Phe464, Met468, Tyr497, Ile494) in an inter-helix space formed with two other α helices (res. Ala461–Phe476 and res. Thr488-Gly502). In the variant simulations, the cyclic five-membered pyrrolidine ring of Pro465 is not as optimal as the side chain of Leu465 for filling the three α helix hydrophobic niche. Although the residue swap does not cause a large-scale conformational shift during the simulations, the H-bond between the backbone amide group of Leu465 and the backbone carbonyl group of Ala461 is lost. This, in turn, breaks the continuity of the α helix secondary structure element.
c.1445T>C	L482P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L482P is not reported in ClinVar and is absent from gnomAD. All available in‑silico predictors classify the substitution as pathogenic: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign effect. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized indicates pathogenicity; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also reports Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts a pathogenic impact. Based on the unanimous computational evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.254060	Structured	0.426236	Uncertain	0.795	0.248	0.000											-12.866	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	3.59	Destabilizing	0.1	10.87	Destabilizing	7.23	Destabilizing	1.55	Destabilizing	0.896	Likely Pathogenic	-6.91	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.30	Pathogenic	0.01	Affected			0.2756	0.0825		-3	-3	-5.4	-16.04
c.1466T>C	L489P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L489P is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. All evaluated in‑silico predictors classify the change as pathogenic: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign effect. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts pathogenic. Overall, the variant is most likely pathogenic based on the consensus of predictive tools, a conclusion that contradicts the current ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.191378	Structured	0.326126	Uncertain	0.949	0.234	0.125					Conflicting		2				-13.520	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	2.50	Destabilizing	0.1	4.69	Destabilizing	3.60	Destabilizing	1.73	Destabilizing	0.939	Likely Pathogenic	-6.74	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.56	Pathogenic	0.00	Affected	3.37	35	0.3673	0.1474		-3	-3	-5.4	-16.04	209.9	61.9	0.1	0.0	0.6	0.1		X						Potentially Pathogenic	The iso-butyl side chain of Leu489, located in the α-helix (res. Leu489-Glu519) within an inter-helix space of four helices (res. Ala461-Phe476, res. Val441-Ser457, and res. Met414-Glu436), packs with hydrophobic residues (e.g., Cys432, Ala448, Lys444, Ala493, Val447, Met468). In the variant simulations, Pro489 is located near the beginning of the α-helix, so the residue swap with Leu489 does not affect the continuity of the secondary structure element. However, the side chain of proline is not as optimal as that of leucine for maintaining hydrophobic packing with nearby residues (e.g., Ala448, Lys444). Additionally, the consistently maintained hydrogen bond interaction between the backbone amide group of Leu489 and the carbonyl of Glu436 is lost due to the residue swap, potentially affecting the tertiary structure integrity.
c.1499T>C	L500P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L500P is listed in ClinVar (ID 2708686.0) as Pathogenic and is not reported in gnomAD. All available in‑silico predictors classify the variant as pathogenic: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign effect. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. Thus, the variant is most likely pathogenic, and this prediction aligns with its ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.066181	Structured	0.382942	Uncertain	0.893	0.150	0.000					Pathogenic		1				-15.898	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	5.91	Destabilizing	0.3	8.90	Destabilizing	7.41	Destabilizing	1.92	Destabilizing	0.894	Likely Pathogenic	-6.96	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.37	Pathogenic	0.01	Affected	3.37	35	0.3103	0.0625		-3	-3	-5.4	-16.04
c.1517T>C	L506P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L506P is listed in ClinVar (ID 975474.0) as Pathogenic and is not reported in gnomAD. All available in‑silico predictors classify the variant as pathogenic: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign effect. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized is Pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) is Pathogenic. Based on the unanimous computational evidence, the variant is most likely pathogenic, which aligns with its ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.034884	Structured	0.279180	Uncertain	0.924	0.196	0.000					Likely Pathogenic		1				-12.088	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	5.48	Destabilizing	0.7	10.19	Destabilizing	7.84	Destabilizing	2.50	Destabilizing	0.737	Likely Pathogenic	-6.96	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	1.55	Pathogenic	0.00	Affected	3.37	35	0.3047	0.0625		-3	-3	-5.4	-16.04	182.6	64.9	0.1	0.0	0.2	0.1	X							Potentially Pathogenic	Leu506 is located in the middle of an α-helix (res. Gly502-Tyr518) within the inter-helix space of two helices (res. Gly502-Tyr518 and res. Glu582-Met603). In the WT simulations, the iso-butyl side chain of Leu506 hydrophobically packs with residues in the inter-helix space (e.g., Ile510, Phe597, Leu598, Ala601). In the variant simulations, the cyclic five-membered pyrrolidine ring of Pro506 is not as optimal as Leu506 for hydrophobic packing with nearby residues. Additionally, Pro506 cannot maintain the hydrogen bond with the backbone oxygen of Gly502 as Leu506 does in the WT, which disrupts the secondary structure element.
c.1550T>C	L517P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L517P is not reported in ClinVar and is absent from gnomAD. Prediction tools uniformly indicate a deleterious effect: pathogenic predictions are returned by REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized classifies the change as pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, labels it likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also reports a pathogenic effect. Consequently, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.118441	Structured	0.147645	Uncertain	0.938	0.296	0.000											-15.546	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	5.88	Destabilizing	0.8	7.96	Destabilizing	6.92	Destabilizing	1.92	Destabilizing	0.937	Likely Pathogenic	-6.70	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.50	Pathogenic	0.00	Affected			0.3570	0.1963		-3	-3	-5.4	-16.04
c.1628T>C	L543P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L543P (ClinVar ID 4540554) is classified as Pathogenic in ClinVar and is not reported in gnomAD. Prediction tools that assess functional impact uniformly indicate a deleterious effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity. No tool in the dataset predicts a benign outcome. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized is Pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) is Pathogenic. All available predictions and stability analyses support a pathogenic effect. Therefore, the variant is most likely pathogenic, and this conclusion is consistent with its ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.048328	Structured	0.020918	Uncertain	0.963	0.314	0.000					Likely Pathogenic		1				-15.958	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	8.56	Destabilizing	0.6	13.44	Destabilizing	11.00	Destabilizing	1.54	Destabilizing	0.770	Likely Pathogenic	-6.97	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	1.89	Pathogenic	0.00	Affected			0.3457	0.0992		-3	-3	-5.4	-16.04
c.1652T>C	L551P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L551P (ClinVar ID 547942.0) is classified as Pathogenic in ClinVar and is not reported in gnomAD. Prediction tools that assess functional impact uniformly indicate a deleterious effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity. No tool in the dataset predicts a benign outcome. High‑accuracy assessments further support this: AlphaMissense‑Optimized is Pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, is Pathogenic. Based on the collective predictions, the variant is most likely pathogenic, and this conclusion aligns with its ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.009977	Structured	0.006653	Uncertain	0.960	0.254	0.000					Likely Pathogenic		1				-14.620	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	6.66	Destabilizing	0.1	6.58	Destabilizing	6.62	Destabilizing	2.66	Destabilizing	0.953	Likely Pathogenic	-4.70	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.60	Pathogenic	0.01	Affected	3.37	35	0.3377	0.1353		-3	-3	-5.4	-16.04	208.6	60.9	0.1	0.0	-0.3	0.0	X							Potentially Pathogenic	L551 is located on an α-helix (res. Ala533-Val560). The iso-butyl side chain of Leu551 hydrophobically packs with nearby hydrophobic residues such as Cys547, Phe652, Leu633, and Ile630 in the inter-helix space. In the variant simulations, the pyrrolidine side chain of Pro551 is not as optimal as leucine for hydrophobic packing with the nearby residues. Moreover, Pro551 lacks the amide group, and thus, it cannot form a hydrogen bond with the backbone carbonyl group of Cys547, which disrupts the continuity of the secondary structure element.
c.167T>C	L56P 2D AIThe SynGAP1 missense variant L56P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Pathogenic. No Foldetta stability prediction is available for this variant. Overall, the preponderance of computational evidence points to a pathogenic effect, and this conclusion is not contradicted by any ClinVar annotation, which is currently absent. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.342579	Structured	0.476218	Uncertain	0.495	0.657	0.000											-9.991	Likely Pathogenic	0.971	Likely Pathogenic	Likely Pathogenic										0.307	Likely Benign	-2.62	Deleterious	0.943	Possibly Damaging	0.944	Probably Damaging	3.77	Benign	0.00	Affected			0.3806	0.1342		-3	-3	-5.4	-16.04
c.1694T>C	L565P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L565P is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that assess pathogenicity largely agree: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a pathogenic effect, while only FATHMM predicts a benign outcome. High‑accuracy assessments reinforce this consensus: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is pathogenic. No prediction or folding‑stability result is missing or inconclusive. Based on the overwhelming agreement among these tools, the variant is most likely pathogenic, and this conclusion does not contradict any existing ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.034884	Structured	0.045819	Uncertain	0.922	0.205	0.000											-13.369	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	3.59	Destabilizing	0.4	6.82	Destabilizing	5.21	Destabilizing	2.33	Destabilizing	0.546	Likely Pathogenic	-6.97	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	2.74	Benign	0.00	Affected			0.3825	0.0877		-3	-3	-5.4	-16.04
c.170T>C	L57P 2D AIThe SynGAP1 missense variant L57P is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM. Tools that agree on a pathogenic effect include polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized predicts pathogenicity. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 pathogenic vs. 2 benign). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of predictions (six pathogenic vs. three benign) indicate that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.254060	Structured	0.481044	Uncertain	0.554	0.642	0.000											-10.724	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic										0.242	Likely Benign	-1.77	Neutral	0.943	Possibly Damaging	0.944	Probably Damaging	3.90	Benign	0.00	Affected			0.3651	0.1703		-3	-3	-5.4	-16.04
c.1721T>C	L574P 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L574P is not reported in ClinVar and is present in gnomAD (6-33440773‑T‑C). Prediction tools that indicate a benign effect include REVEL, PROVEAN, and SIFT, whereas the majority of tools predict a pathogenic impact: FoldX, Rosetta, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, Foldetta, and the SGM Consensus score (likely pathogenic). High‑accuracy methods specifically give a pathogenic verdict: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Based on the collective evidence, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.083462	Structured	0.026427	Uncertain	0.927	0.246	0.000								6-33440773-T-C			-13.394	Likely Pathogenic	0.989	Likely Pathogenic	Likely Pathogenic	2.95	Destabilizing	0.5	9.19	Destabilizing	6.07	Destabilizing	0.59	Ambiguous	0.442	Likely Benign	-1.05	Neutral	1.000	Probably Damaging	0.971	Probably Damaging	-1.29	Pathogenic	0.26	Tolerated	3.38	32	0.3811	0.0953		-3	-3	-5.4	-16.04
c.1763T>C	L588P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L588P is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. All available in silico predictors classify the change as pathogenic: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign effect. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts pathogenicity. Consequently, the variant is most likely pathogenic based on the collective predictions, and this assessment does not contradict the ClinVar status, which remains uncertain. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.038042	Structured	0.082229	Uncertain	0.887	0.214	0.000					Uncertain		2				-14.771	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	5.61	Destabilizing	0.5	12.91	Destabilizing	9.26	Destabilizing	2.33	Destabilizing	0.932	Likely Pathogenic	-6.97	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.42	Pathogenic	0.00	Affected	3.38	34	0.3533	0.0992		-3	-3	-5.4	-16.04
c.176T>C	L59P 2D AIThe SynGAP1 missense variant L59P is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect are REVEL and FATHMM, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. ESM1b is uncertain. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a pathogenic verdict (2 pathogenic vs. 1 benign). Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.212910	Structured	0.484882	Uncertain	0.510	0.668	0.000											-7.076	In-Between	0.993	Likely Pathogenic	Likely Pathogenic										0.362	Likely Benign	-2.74	Deleterious	0.943	Possibly Damaging	0.944	Probably Damaging	3.25	Benign	0.00	Affected			0.3787	0.1382		-3	-3	-5.4	-16.04
c.1778T>C	L593P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L593P is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include only FATHMM, whereas all other evaluated algorithms (SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) predict a pathogenic outcome. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized scores the variant as pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, also classifies the variant as pathogenic. Based on the overwhelming consensus of pathogenic predictions, the variant is most likely pathogenic, a conclusion that contradicts its current ClinVar “Uncertain” status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.009728	Structured	0.110534	Uncertain	0.941	0.151	0.000					Uncertain		1				-13.961	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	5.75	Destabilizing	0.9	10.77	Destabilizing	8.26	Destabilizing	2.43	Destabilizing	0.777	Likely Pathogenic	-6.77	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	2.77	Benign	0.00	Affected			0.3783	0.1274		-3	-3	-5.4	-16.04
c.1784T>C	L595P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L595P is listed in ClinVar with an “Uncertain” status (ClinVar ID 3172762.0) and is not reported in gnomAD. Prediction tools that agree on a benign effect include only FATHMM, whereas all other evaluated algorithms (REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) predict a pathogenic outcome. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. No prediction or folding stability result is missing or inconclusive. Based on the collective evidence, the variant is most likely pathogenic, which does not contradict the current ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.015344	Structured	0.128444	Uncertain	0.920	0.150	0.000					Uncertain		1				-11.856	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	2.09	Destabilizing	0.8	5.88	Destabilizing	3.99	Destabilizing	1.78	Destabilizing	0.747	Likely Pathogenic	-6.97	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	2.72	Benign	0.00	Affected	3.37	35	0.3336	0.1713		-3	-3	-5.4	-16.04
c.1793T>C	L598P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L598P is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a deleterious effect: pathogenic predictions come from SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only FATHMM predicts a benign outcome. High‑accuracy methods reinforce the pathogenic view: AlphaMissense‑Optimized scores the variant as pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates it is likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also classifies it as pathogenic. No prediction or stability result is missing or inconclusive. Based on the consensus of these tools, the variant is most likely pathogenic, and this assessment is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.007259	Structured	0.147872	Uncertain	0.953	0.154	0.000											-12.621	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	8.31	Destabilizing	0.5	12.04	Destabilizing	10.18	Destabilizing	2.02	Destabilizing	0.705	Likely Pathogenic	-6.87	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.10	Benign	0.00	Affected			0.2742	0.1192		-3	-3	-5.4	-16.04
c.1820T>C	L607P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L607P is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess pathogenicity uniformly indicate a deleterious effect: REVEL, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as pathogenic, while the SGM‑Consensus score is “Likely Pathogenic.” No tool in the dataset predicts a benign outcome; the only inconclusive result is FoldX, which is listed as uncertain and therefore does not influence the overall assessment. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenicity. Consequently, the variant is most likely pathogenic based on the available predictions, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.048328	Structured	0.194229	Uncertain	0.869	0.250	0.000											-14.059	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	1.11	Ambiguous	0.7	6.93	Destabilizing	4.02	Destabilizing	1.29	Destabilizing	0.922	Likely Pathogenic	-6.97	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.54	Pathogenic	0.00	Affected			0.3710	0.1274		-3	-3	-5.4	-16.04
c.1829T>C	L610P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L610P is not reported in ClinVar and is absent from gnomAD. Across the available in‑silico predictors, every tool examined (REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) classifies the substitution as pathogenic; no tool predicts a benign effect. High‑accuracy methods reinforce this consensus: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also reports a pathogenic effect. Because all evidence points to a deleterious impact and there is no ClinVar entry to contradict this, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.271506	Structured	0.209504	Uncertain	0.888	0.253	0.000											-14.863	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic	6.02	Destabilizing	0.2	8.15	Destabilizing	7.09	Destabilizing	1.99	Destabilizing	0.934	Likely Pathogenic	-6.91	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.59	Pathogenic	0.00	Affected			0.3599	0.1113		-3	-3	-5.4	-16.04
c.1868T>C	L623P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L623P is not reported in ClinVar and is absent from gnomAD. Prediction tools uniformly indicate a deleterious effect: pathogenic predictions are returned by REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized classifies the change as pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, labels it likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also reports a pathogenic effect. Consequently, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.175930	Structured	0.060667	Uncertain	0.962	0.211	0.000											-12.385	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	6.70	Destabilizing	0.2	11.18	Destabilizing	8.94	Destabilizing	2.26	Destabilizing	0.788	Likely Pathogenic	-6.97	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	1.56	Pathogenic	0.00	Affected			0.3961	0.1474		-3	-3	-5.4	-16.04
c.1874T>C	L625P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L625P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only FATHMM, whereas the remaining 13 tools (SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) uniformly predict a pathogenic impact. High‑accuracy methods give consistent results: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts pathogenic. No prediction or stability result is missing or inconclusive. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.229226	Structured	0.045896	Uncertain	0.966	0.215	0.000											-14.819	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	5.47	Destabilizing	0.6	12.49	Destabilizing	8.98	Destabilizing	1.98	Destabilizing	0.746	Likely Pathogenic	-6.92	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	2.98	Benign	0.00	Affected			0.3294	0.1313		-3	-3	-5.4	-16.04
c.1898T>C	L633P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L633P (ClinVar ID 858973.0) is listed as Pathogenic and is not reported in gnomAD. Prediction tools that classify the variant as benign include only FATHMM. All other evaluated tools—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict it to be pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized scores it as Pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, predicts Pathogenic. Based on the overwhelming consensus of pathogenic predictions and the ClinVar designation, the variant is most likely pathogenic, with no contradiction to its ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.045352	Structured	0.045407	Uncertain	0.952	0.252	0.000					Pathogenic/Likely path.		2				-15.669	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	6.60	Destabilizing	0.2	10.15	Destabilizing	8.38	Destabilizing	2.42	Destabilizing	0.693	Likely Pathogenic	-6.97	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	2.70	Benign	0.00	Affected	3.37	34	0.3528	0.0953		-3	-3	-5.4	-16.04	193.2	65.1	0.0	0.0	0.1	0.0	X							Potentially Pathogenic	The iso-butyl side chain of Leu633, located in the middle of an α helix (res. Glu617-Asn635), packs hydrophobically with nearby residues (e.g., Leu653, Val629, Leu551) in the WT simulations.In the variant simulations, the pyrrolidine side chain of Pro633 is not as optimal for hydrophobic packing as Leu633 in the WT. Additionally, proline lacks a free backbone amide group, so Pro633 cannot form a hydrogen bond with the backbone carbonyl group of Val629, which disrupts the continuity of the secondary structure element.
c.1937T>C	L646P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L646P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only FATHMM, whereas all other evaluated algorithms—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. High‑accuracy methods further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. No prediction or folding stability result is missing or inconclusive. Based on the overwhelming consensus of pathogenic predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued in ClinVar. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.048328	Structured	0.303751	Uncertain	0.941	0.344	0.000											-12.956	Likely Pathogenic	0.970	Likely Pathogenic	Likely Pathogenic	7.34	Destabilizing	0.5	12.08	Destabilizing	9.71	Destabilizing	2.72	Destabilizing	0.604	Likely Pathogenic	-4.55	Deleterious	0.999	Probably Damaging	0.926	Probably Damaging	3.17	Benign	0.00	Affected			0.3481	0.1874		-3	-3	-5.4	-16.04
c.1958T>C	L653P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L653P is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include only FATHMM, whereas the remaining tools—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy methods give the following results: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. Based on the overwhelming agreement among these tools, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.049374	Structured	0.335213	Uncertain	0.963	0.332	0.000											-17.675	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	6.02	Destabilizing	0.8	9.20	Destabilizing	7.61	Destabilizing	2.56	Destabilizing	0.700	Likely Pathogenic	-6.51	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.09	Benign	0.00	Affected			0.3251	0.1874		-3	-3	-5.4	-16.04
c.1964T>C	L655P 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L655P is catalogued in gnomAD (ID 6‑33441223‑T‑C) but has no ClinVar entry. Functional prediction tools show a split: benign calls come from REVEL, PROVEAN, SIFT, and FATHMM, whereas pathogenic calls are made by Rosetta, Foldetta, both polyPhen‑2 versions, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; FoldX and premPS are uncertain. High‑accuracy assessments give AlphaMissense‑Optimized as pathogenic, Foldetta as pathogenic, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive. Overall, the majority of evidence points to a pathogenic effect. This conclusion is consistent with the absence of a ClinVar classification, so there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.015344	Structured	0.268808	Uncertain	0.961	0.274	0.000								6-33441223-T-C	1	6.20e-7	-9.771	Likely Pathogenic	0.982	Likely Pathogenic	Likely Pathogenic	1.33	Ambiguous	0.5	6.52	Destabilizing	3.93	Destabilizing	0.57	Ambiguous	0.126	Likely Benign	-1.36	Neutral	0.981	Probably Damaging	0.772	Possibly Damaging	3.47	Benign	0.32	Tolerated	3.39	24	0.3598	0.1274		-3	-3	-5.4	-16.04
c.2009T>C	L670P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L670P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all indicate benign. In contrast, polyPhen‑2 (HumDiv and HumVar) predict a pathogenic impact. Stability‑based methods are inconclusive: FoldX, Rosetta, and the combined Foldetta output are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely benign, and Foldetta as uncertain. Overall, the majority of evidence supports a benign classification, and this is consistent with the absence of a ClinVar assertion; there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.161087	Structured	0.090855	Uncertain	0.812	0.385	0.000											-4.916	Likely Benign	0.237	Likely Benign	Likely Benign	0.56	Ambiguous	0.3	1.83	Ambiguous	1.20	Ambiguous	-0.25	Likely Benign	0.211	Likely Benign	2.42	Neutral	1.000	Probably Damaging	0.996	Probably Damaging	3.41	Benign	0.26	Tolerated			0.3590	0.1474		-3	-3	-5.4	-16.04
c.200T>C	L67P 2D AIThe SynGAP1 missense variant L67P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as “Uncertain” and the SGM‑Consensus as “Likely Benign”; Foldetta results are unavailable. Overall, the majority of evidence points toward a benign impact. The variant’s predicted benign status does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.458154	Structured	0.473668	Uncertain	0.428	0.761	0.125											-2.852	Likely Benign	0.945	Likely Pathogenic	Ambiguous										0.150	Likely Benign	-0.80	Neutral	0.943	Possibly Damaging	0.766	Possibly Damaging	4.07	Benign	0.00	Affected			0.3052	0.1382		-3	-3	-5.4	-16.04
c.2018T>C	L673P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L673P is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized. All other evaluated tools—SGM‑Consensus, FoldX, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default—predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized indicates benign, but the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) resolves as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts Pathogenic. Taken together, the overwhelming majority of predictions, including the high‑accuracy tools, classify the variant as pathogenic. This conclusion is not contradicted by ClinVar, which contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.060549	Structured	0.104692	Uncertain	0.545	0.369	0.000											-12.160	Likely Pathogenic	0.622	Likely Pathogenic	Likely Benign	2.41	Destabilizing	0.3	1.63	Ambiguous	2.02	Destabilizing	1.17	Destabilizing	0.207	Likely Benign	-4.10	Deleterious	1.000	Probably Damaging	0.978	Probably Damaging	3.37	Benign	0.02	Affected			0.3552	0.1474		-3	-3	-5.4	-16.04
c.203T>C	L68P 2D AIThe SynGAP1 missense variant L68P is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL, PROVEAN, ESM1b, FATHMM, and the SGM‑Consensus (Likely Benign). Tools that predict pathogenicity are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of predictions lean toward pathogenic, but the consensus from SGM and the high‑accuracy AlphaMissense‑Optimized are contradictory, leaving the variant’s clinical significance uncertain. No conflict exists with ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.534167	Disordered	0.470567	Uncertain	0.405	0.768	0.250											-2.122	Likely Benign	0.956	Likely Pathogenic	Likely Pathogenic										0.143	Likely Benign	-0.57	Neutral	0.943	Possibly Damaging	0.766	Possibly Damaging	4.09	Benign	0.00	Affected			0.2827	0.1382		-3	-3	-5.4	-16.04
c.2066T>C	L689P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L689P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only FATHMM, whereas all other evaluated algorithms—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. High‑accuracy methods further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. No prediction or folding stability result is missing or inconclusive. Based on the overwhelming consensus of pathogenic predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.042364	Structured	0.227227	Uncertain	0.963	0.248	0.000											-17.900	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	6.76	Destabilizing	0.2	13.35	Destabilizing	10.06	Destabilizing	2.29	Destabilizing	0.631	Likely Pathogenic	-6.97	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.17	Benign	0.00	Affected			0.3668	0.1353		-3	-3	-5.4	-16.04
c.2075T>C	L692P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L692P is listed in ClinVar with an “Uncertain” status (ClinVar ID 847082.0) and is not reported in gnomAD. Prediction tools that agree on a benign effect are limited to FATHMM, while the remaining tools (REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) uniformly predict a pathogenic impact. High‑accuracy assessments further support this: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts pathogenic. Based on the overwhelming consensus of pathogenic predictions, the variant is most likely pathogenic, which does not contradict its current ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.064632	Structured	0.295225	Uncertain	0.966	0.243	0.000					Uncertain		1				-16.447	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	9.19	Destabilizing	0.1	13.20	Destabilizing	11.20	Destabilizing	1.69	Destabilizing	0.668	Likely Pathogenic	-6.98	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.06	Benign	0.00	Affected	3.42	17	0.3642	0.1025		-3	-3	-5.4	-16.04	186.2	62.8	-0.2	0.1	-0.7	0.3	X							Potentially Pathogenic	The isobutyl side chain of Leu692, located in the middle of an α-helix (res. Leu685-Gln702), engages in hydrophobic packing with nearby residues (e.g., Leu441, Leu431, Leu696) in the inter-helix space. Prolines lack a free amide group necessary for hydrogen bonding with the carbonyl group of Glu688 in the same manner as Leu692 in the WT. Consequently, the residue swap with proline disrupts the continuity of the secondary structure element in the variant simulations. Additionally, the side chain of Pro692 is not as optimal as Leu692 for hydrophobic packing in the inter-helix space.
c.2084T>C	L695P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L695P is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include only FATHMM, whereas the remaining tools—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy methods give the following results: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenic. Based on the overwhelming agreement among these tools, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.118441	Structured	0.373419	Uncertain	0.942	0.258	0.000											-17.496	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	4.63	Destabilizing	0.2	4.73	Destabilizing	4.68	Destabilizing	2.11	Destabilizing	0.612	Likely Pathogenic	-6.85	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.16	Benign	0.00	Affected			0.3044	0.0992		-3	-3	-5.4	-16.04
c.2087T>C	L696P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L696P is listed in ClinVar as Pathogenic (ClinVar ID 1699350.0) and is not reported in gnomAD. Prediction tools that classify the variant as benign include only FATHMM; all other evaluated algorithms—REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—report it as pathogenic. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a pathogenic effect. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote) is pathogenic, and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, predicts a destabilizing, pathogenic outcome. Taken together, the overwhelming majority of predictions and the high‑accuracy tools classify the variant as pathogenic, fully consistent with its ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.200174	Structured	0.390093	Uncertain	0.962	0.267	0.000					Likely Pathogenic		1				-16.926	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	6.66	Destabilizing	0.2	10.84	Destabilizing	8.75	Destabilizing	2.13	Destabilizing	0.678	Likely Pathogenic	-6.58	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.00	Benign	0.00	Affected	3.46	13	0.3065	0.1995		-3	-3	-5.4	-16.04	180.6	65.9	0.1	0.0	-0.6	0.1	X							Potentially Pathogenic	The isobutyl side chain of Leu696, located in the middle of an α-helix (res. Leu685-Gln702), engages in hydrophobic packing with nearby residues (e.g., Leu441, Leu431, Leu692, Leu714) in the inter-helix space. Prolines lack a free amide group necessary for hydrogen bonding with the carbonyl group of Leu692 in the same manner as Leu696 in the WT. Consequently, the residue swap with proline disrupts the continuity of the secondary structure element in the variant simulations. Additionally, the side chain of Pro696 is not as optimal as Leu696 for hydrophobic packing in the inter-helix space.
c.2099T>C	L700P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L700P is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a deleterious effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as pathogenic, while only FATHMM predicts it benign. The SGM‑Consensus, which is a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a “Likely Pathogenic” verdict (3 pathogenic vs. 1 benign). High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is pathogenic, SGM‑Consensus is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. No prediction or stability result is missing or inconclusive. Based on the overwhelming consensus of pathogenic predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.113710	Structured	0.416255	Uncertain	0.927	0.331	0.000											-13.092	Likely Pathogenic	0.982	Likely Pathogenic	Likely Pathogenic	7.29	Destabilizing	0.5	12.85	Destabilizing	10.07	Destabilizing	1.84	Destabilizing	0.541	Likely Pathogenic	-4.31	Deleterious	0.999	Probably Damaging	0.966	Probably Damaging	3.30	Benign	0.01	Affected			0.3603	0.1025		-3	-3	-5.4	-16.04
c.2108T>C	L703P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L703P is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a deleterious effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as pathogenic, while only FATHMM predicts it benign. The SGM‑Consensus, which is a majority vote among AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a “Likely Pathogenic” result (3 pathogenic vs. 1 benign). High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is pathogenic; SGM‑Consensus is likely pathogenic; and Foldetta, integrating FoldX‑MD and Rosetta outputs, is pathogenic. No prediction or stability result is missing or inconclusive. Based on the overwhelming consensus of pathogenic predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.144935	Structured	0.388282	Uncertain	0.929	0.353	0.000											-13.766	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic	4.44	Destabilizing	0.1	9.38	Destabilizing	6.91	Destabilizing	1.54	Destabilizing	0.559	Likely Pathogenic	-5.70	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.11	Benign	0.00	Affected			0.3698	0.1186		-3	-3	-5.4	-16.04
c.2123T>C	L708P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L708P is not reported in ClinVar and is absent from gnomAD. Consensus among most in‑silico predictors is strongly pathogenic: FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all indicate a deleterious effect. Only REVEL and FATHMM predict a benign outcome, while AlphaMissense‑Optimized is uncertain. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is inconclusive, SGM Consensus reports “Likely Pathogenic,” and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a destabilizing, pathogenic change. Taken together, the preponderance of evidence points to a pathogenic impact for L708P, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.250310	Structured	0.365875	Uncertain	0.931	0.378	0.000											-10.268	Likely Pathogenic	0.932	Likely Pathogenic	Ambiguous	4.29	Destabilizing	0.1	6.43	Destabilizing	5.36	Destabilizing	1.62	Destabilizing	0.298	Likely Benign	-4.47	Deleterious	1.000	Probably Damaging	0.989	Probably Damaging	3.39	Benign	0.04	Affected			0.2800	0.0825		-3	-3	-5.4	-16.04
c.2126T>C	L709P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L709P is not reported in ClinVar and is absent from gnomAD. Benign predictions come from REVEL, premPS, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions arise from FoldX, Rosetta, Foldetta, polyPhen2_HumDiv, polyPhen2_HumVar, and AlphaMissense‑Default. High‑accuracy tools give mixed results: AlphaMissense‑Optimized predicts benign; the SGM Consensus (majority vote of AlphaMissense‑Default, FATHMM, PROVEAN) also predicts benign; Foldetta predicts pathogenic. Because the majority of standard predictors and the SGM Consensus favor benign, the variant is most likely benign, and this is consistent with the lack of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.243554	Structured	0.365830	Uncertain	0.934	0.379	0.000											-7.517	In-Between	0.767	Likely Pathogenic	Likely Benign	2.81	Destabilizing	0.0	5.65	Destabilizing	4.23	Destabilizing	0.31	Likely Benign	0.167	Likely Benign	-1.93	Neutral	1.000	Probably Damaging	0.975	Probably Damaging	3.47	Benign	0.37	Tolerated			0.3004	0.0825		-3	-3	-5.4	-16.04
c.2132T>C	L711P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense change L711P is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are REVEL and FATHMM; all other evaluated algorithms—including FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized scores the variant as pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic outcome; and Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, also classifies the variant as pathogenic. Based on the overwhelming agreement among these tools, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.308712	Structured	0.377436	Uncertain	0.950	0.364	0.000											-12.128	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	5.70	Destabilizing	0.1	8.15	Destabilizing	6.93	Destabilizing	2.09	Destabilizing	0.375	Likely Benign	-6.59	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.28	Benign	0.00	Affected			0.3300	0.0986		-3	-3	-5.4	-16.04
c.2141T>C	L714P 2D AIThe SynGAP1 missense variant L714P is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect are REVEL and FATHMM, whereas the remaining tools—FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized scores the variant as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic outcome; and Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, also classifies the variant as pathogenic. Based on the preponderance of evidence from these tools, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.314870	Structured	0.402311	Uncertain	0.961	0.369	0.000											-12.562	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	7.48	Destabilizing	1.9	13.54	Destabilizing	10.51	Destabilizing	2.26	Destabilizing	0.441	Likely Benign	-6.44	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.08	Benign	0.00	Affected			0.3572	0.1253		-3	-3	-5.4	-16.04
c.2150T>C	L717P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L717P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: benign predictions come from REVEL and FATHMM, while the remaining 13 tools (FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus) all classify the variant as pathogenic. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts a pathogenic effect. No predictions are missing or inconclusive. Based on the preponderance of evidence, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.239899	Structured	0.429342	Uncertain	0.969	0.397	0.000											-10.214	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	3.96	Destabilizing	0.2	6.56	Destabilizing	5.26	Destabilizing	1.66	Destabilizing	0.447	Likely Benign	-5.32	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.28	Benign	0.00	Affected			0.3065	0.1053		-3	-3	-5.4	-16.04
c.2153T>C	L718P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L718P is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess pathogenicity are unanimous: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as pathogenic. No tool in the dataset predicts a benign effect, so the benign‑prediction group is empty. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenic. Consequently, the variant is most likely pathogenic based on the available predictions, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.298791	Structured	0.438417	Uncertain	0.966	0.385	0.000											-15.643	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	6.56	Destabilizing	0.1	9.69	Destabilizing	8.13	Destabilizing	2.35	Destabilizing	0.660	Likely Pathogenic	-6.64	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	1.28	Pathogenic	0.00	Affected			0.3854	0.1221		-3	-3	-5.4	-16.04
c.2174T>C	L725P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L725P is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated tools—FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—classify the variant as pathogenic or likely pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus (majority vote) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. No prediction or folding stability result is missing or inconclusive. **Based on the collective predictions, the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which is currently unreported.** Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.557691	Disordered	0.455613	Uncertain	0.911	0.491	0.625											-15.390	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	4.91	Destabilizing	0.1	9.02	Destabilizing	6.97	Destabilizing	1.82	Destabilizing	0.396	Likely Benign	-6.08	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	1.28	Pathogenic	0.00	Affected			0.3796	0.1664		-3	-3	-5.4	-16.04
c.2243T>C	L748P 2D AIThe SynGAP1 missense variant L748P is reported in gnomAD (ID 6‑33441708‑T‑C) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Pathogenic predictions are made by polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. High‑accuracy assessments reinforce the benign view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields benign. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the preponderance of evidence from both general and high‑accuracy tools indicates that the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none is assigned). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.703578	Disordered	0.611637	Binding	0.339	0.863	0.750								6-33441708-T-C	1	6.20e-7	-2.732	Likely Benign	0.129	Likely Benign	Likely Benign										0.075	Likely Benign	-0.69	Neutral	0.912	Possibly Damaging	0.611	Possibly Damaging	2.69	Benign	0.02	Affected	4.32	2	0.3503	0.1399		-3	-3	-5.4	-16.04
c.2288T>C	L763P 2D AIThe SynGAP1 missense variant L763P is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. AlphaMissense‑Default is uncertain. For high‑accuracy assessment, AlphaMissense‑Optimized predicts benign. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also yields a benign prediction (2 benign vs. 1 pathogenic, with one uncertain). Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.380708	Structured	0.918636	Binding	0.351	0.865	0.125											-5.802	Likely Benign	0.550	Ambiguous	Likely Benign										0.158	Likely Benign	-0.89	Neutral	0.999	Probably Damaging	0.977	Probably Damaging	2.36	Pathogenic	0.12	Tolerated			0.3920	0.1182		-3	-3	-5.4	-16.04
c.2306T>C	L769P 2D AIThe SynGAP1 missense variant L769P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign impact for this variant, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.411940	Structured	0.928432	Binding	0.367	0.883	0.250											-6.261	Likely Benign	0.338	Likely Benign	Likely Benign										0.200	Likely Benign	-1.75	Neutral	0.925	Possibly Damaging	0.427	Benign	3.90	Benign	0.00	Affected			0.3573	0.1323		-3	-3	-5.4	-16.04
c.2330T>C	L777P 2D AIThe SynGAP1 missense variant L777P is catalogued in gnomAD (6‑33442488‑T‑C) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Pathogenic predictions are reported by polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments reinforce the benign trend: AlphaMissense‑Optimized scores the variant as benign, and the SGM‑Consensus also indicates a likely benign outcome. No Foldetta stability analysis is available, so it does not influence the assessment. Overall, the preponderance of evidence points to a benign effect for the variant, and this conclusion is not contradicted by any ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.408655	Structured	0.876129	Binding	0.336	0.882	0.250								6-33442488-T-C			-5.807	Likely Benign	0.361	Ambiguous	Likely Benign										0.255	Likely Benign	-2.13	Neutral	0.991	Probably Damaging	0.985	Probably Damaging	3.94	Benign	0.00	Affected	3.64	6	0.3732	0.1664		-3	-3	-5.4	-16.04
c.2357T>C	L786P 2D AISynGAP1 missense variant L786P is reported in gnomAD (ID 6‑33442909‑T‑C) but has no ClinVar entry. Functional prediction tools show discordant results: benign predictions come from REVEL, ESM1b, and AlphaMissense‑Optimized, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further highlight this split: AlphaMissense‑Optimized reports a benign effect, SGM‑Consensus confirms a likely pathogenic outcome, and Foldetta results are unavailable. Overall, the majority of conventional tools and the SGM‑Consensus support a pathogenic interpretation, while one high‑accuracy tool suggests benign. No ClinVar status is present, so there is no contradiction with existing clinical annotations. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.882776	Disordered	0.655253	Binding	0.341	0.895	0.750								6-33442909-T-C			-3.217	Likely Benign	0.656	Likely Pathogenic	Likely Benign										0.219	Likely Benign	-4.06	Deleterious	0.999	Probably Damaging	0.999	Probably Damaging	1.79	Pathogenic	0.00	Affected	3.77	5	0.3343	0.1814		-3	-3	-5.4	-16.04
c.2414T>C	L805P 2D AIThe SynGAP1 missense variant L805P is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Functional prediction tools show a split: benign calls come from REVEL, ESM1b, and AlphaMissense‑Optimized, while pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM; AlphaMissense‑Default remains uncertain. High‑accuracy assessments give a benign result from AlphaMissense‑Optimized, a pathogenic outcome from the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and no Foldetta data are available. Overall, the majority of predictions lean toward pathogenicity, and this conclusion does not conflict with the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.775545	Disordered	0.827669	Binding	0.341	0.903	0.625					Uncertain		1				-4.661	Likely Benign	0.444	Ambiguous	Likely Benign										0.272	Likely Benign	-3.40	Deleterious	0.975	Probably Damaging	0.767	Possibly Damaging	2.36	Pathogenic	0.00	Affected	3.77	5	0.3128	0.1650		-3	-3	-5.4	-16.04
c.242T>C	L81P 2D AIThe SynGAP1 missense variant L81P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) is not available for this variant. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.632174	Disordered	0.502033	Binding	0.291	0.878	0.250											-4.413	Likely Benign	0.827	Likely Pathogenic	Ambiguous										0.095	Likely Benign	-1.51	Neutral	0.919	Possibly Damaging	0.226	Benign	3.92	Benign	0.00	Affected			0.3062	0.1818		-3	-3	-5.4	-16.04
c.2438T>C	L813P 2D AIThe SynGAP1 missense variant L813P is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in silico tools cluster around a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all indicate benign, while the majority of high‑accuracy predictors (AlphaMissense‑Optimized and the SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also support a benign classification. In contrast, polyPhen‑2 (HumDiv and HumVar) predict a pathogenic impact, and AlphaMissense‑Default remains uncertain. No Foldetta stability assessment is available, so it does not influence the overall interpretation. Overall, the preponderance of evidence points to a benign effect for the variant, and this conclusion is not contradicted by any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.411940	Structured	0.838481	Binding	0.292	0.905	0.250											-2.572	Likely Benign	0.554	Ambiguous	Likely Benign										0.122	Likely Benign	-1.96	Neutral	0.999	Probably Damaging	0.985	Probably Damaging	2.58	Benign	0.21	Tolerated			0.3564	0.1458		-3	-3	-5.4	-16.04
c.245T>C	L82P 2D AIThe SynGAP1 missense variant L82P is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (ID 6‑33425853‑T‑C). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized; ESM1b remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic and the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also favors pathogenicity. Foldetta, a protein‑folding stability method, did not provide a result for this variant. Overall, the majority of evidence points to a pathogenic impact. This conclusion is not contradicted by ClinVar status, which has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.637480	Disordered	0.517720	Binding	0.284	0.890	0.375								6-33425853-T-C	1	6.20e-7	-7.667	In-Between	0.991	Likely Pathogenic	Likely Pathogenic										0.125	Likely Benign	-2.73	Deleterious	0.939	Possibly Damaging	0.162	Benign	3.64	Benign	0.00	Affected	4.32	1	0.3477	0.1118		-3	-3	-5.4	-16.04
c.2504T>C	L835P 2D AIThe SynGAP1 missense variant L835P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability result is available, so it does not influence the overall assessment. Overall, the majority of evidence points to the variant being most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.608892	Disordered	0.642742	Binding	0.319	0.863	0.125											-3.024	Likely Benign	0.139	Likely Benign	Likely Benign										0.144	Likely Benign	0.03	Neutral	0.999	Probably Damaging	0.977	Probably Damaging	2.78	Benign	0.04	Affected			0.3455	0.1079		-3	-3	-5.4	-16.04
c.2531T>C	L844P 2D AIThe SynGAP1 missense variant L844P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Consensus from standard in‑silico predictors shows a split: benign calls come from REVEL and FATHMM, whereas pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized; ESM1b remains uncertain. High‑accuracy assessment further supports a deleterious effect: AlphaMissense‑Optimized predicts pathogenic, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) resolves to pathogenic. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the preponderance of evidence from both conventional and high‑accuracy tools indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.595080	Disordered	0.611301	Binding	0.304	0.835	0.375											-7.425	In-Between	0.962	Likely Pathogenic	Likely Pathogenic										0.319	Likely Benign	-3.18	Deleterious	0.986	Probably Damaging	0.876	Possibly Damaging	2.58	Benign	0.01	Affected			0.3528	0.1458		-3	-3	-5.4	-16.04
c.2564T>C	L855P 2D AIThe SynGAP1 missense variant L855P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv indicates a pathogenic effect. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also predicts benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of the majority of prediction tools and the high‑accuracy methods indicates that the variant is most likely benign, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.724957	Disordered	0.485558	Uncertain	0.285	0.823	0.625											-2.434	Likely Benign	0.092	Likely Benign	Likely Benign										0.116	Likely Benign	-1.19	Neutral	0.586	Possibly Damaging	0.377	Benign	3.97	Benign	0.14	Tolerated			0.3633	0.1805		-3	-3	-5.4	-16.04
c.2588T>C	L863P 2D AIThe SynGAP1 missense variant L863P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict it to be pathogenic. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.525368	Disordered	0.594839	Binding	0.267	0.795	0.250											-4.760	Likely Benign	0.234	Likely Benign	Likely Benign										0.202	Likely Benign	-0.78	Neutral	0.999	Probably Damaging	0.977	Probably Damaging	4.01	Benign	0.12	Tolerated			0.3520	0.1458		-3	-3	-5.4	-16.04
c.2606T>C	L869P 2D AIThe SynGAP1 missense variant L869P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. AlphaMissense‑Default remains uncertain. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a “Likely Benign” classification, and AlphaMissense‑Optimized independently predicts benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence—including the high‑accuracy tools—supports a benign interpretation. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.501700	Disordered	0.688653	Binding	0.272	0.839	0.250											-2.394	Likely Benign	0.523	Ambiguous	Likely Benign										0.174	Likely Benign	-0.99	Neutral	0.990	Probably Damaging	0.900	Possibly Damaging	2.58	Benign	0.04	Affected			0.3687	0.1503		-3	-3	-5.4	-16.04
c.2609T>C	L870P 2D AIThe SynGAP1 missense variant L870P is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. AlphaMissense‑Default is uncertain, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Based on the collective predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.483068	Structured	0.688079	Binding	0.274	0.850	0.125											-4.462	Likely Benign	0.402	Ambiguous	Likely Benign										0.194	Likely Benign	-1.92	Neutral	0.999	Probably Damaging	0.999	Probably Damaging	2.59	Benign	0.13	Tolerated			0.3795	0.1864		-3	-3	-5.4	-16.04
c.2630T>C	L877P 2D AIThe SynGAP1 missense variant L877P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability analysis is available for this variant. Overall, the majority of computational evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.653063	Disordered	0.634010	Binding	0.265	0.875	0.250											-4.960	Likely Benign	0.312	Likely Benign	Likely Benign										0.154	Likely Benign	-1.57	Neutral	0.986	Probably Damaging	0.876	Possibly Damaging	2.59	Benign	0.03	Affected			0.3899	0.1543		-3	-3	-5.4	-16.04
c.2648T>C	L883P 2D AIThe SynGAP1 missense variant L883P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely benign outcome. In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict a pathogenic effect. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the preponderance of evidence supports a benign classification for this variant, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.716283	Disordered	0.641952	Binding	0.334	0.886	0.250											-2.572	Likely Benign	0.105	Likely Benign	Likely Benign										0.074	Likely Benign	-0.58	Neutral	0.934	Possibly Damaging	0.516	Possibly Damaging	2.62	Benign	0.21	Tolerated			0.3462	0.1658		-3	-3	-5.4	-16.04
c.2672T>C	L891P 2D AIThe SynGAP1 missense variant L891P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is “Likely Benign”). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely benign outcome. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect for L891P, and this conclusion is not contradicted by any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.712013	Disordered	0.505861	Binding	0.305	0.923	0.750											-3.835	Likely Benign	0.169	Likely Benign	Likely Benign										0.126	Likely Benign	-1.61	Neutral	0.990	Probably Damaging	0.900	Possibly Damaging	2.67	Benign	0.01	Affected			0.3594	0.1138		-3	-3	-5.4	-16.04
c.2717T>C	L906P 2D AIThe SynGAP1 missense variant L906P is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also favors a benign outcome. Foldetta, which would provide a protein‑folding stability estimate, is unavailable for this variant. Overall, the preponderance of evidence points to a benign impact. This conclusion is not contradicted by ClinVar, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.604312	Disordered	0.644316	Binding	0.315	0.920	0.250											-3.662	Likely Benign	0.478	Ambiguous	Likely Benign										0.150	Likely Benign	0.08	Neutral	1.000	Probably Damaging	0.993	Probably Damaging	2.18	Pathogenic	0.10	Tolerated			0.3430	0.1458		-3	-3	-5.4	-16.04
c.2762T>C	L921P 2D AIThe SynGAP1 missense variant L921P is recorded in gnomAD (ID 6‑33443314‑T‑C) but has no ClinVar submission. Functional prediction tools cluster into two groups: benign calls from REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized; pathogenic calls from polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. AlphaMissense‑Default is uncertain. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive because the votes are split (two benign, one pathogenic, one uncertain). Foldetta, a protein‑folding stability predictor that combines FoldX‑MD and Rosetta outputs, has no reported result for this variant. Consequently, the evidence is evenly divided, with high‑accuracy tools not providing a decisive verdict. The variant is therefore inconclusive; it does not contradict ClinVar status, which currently has no entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.608892	Disordered	0.943282	Binding	0.311	0.845	0.375								6-33443314-T-C	1	6.20e-7	-2.087	Likely Benign	0.393	Ambiguous	Likely Benign										0.215	Likely Benign	-1.83	Neutral	0.998	Probably Damaging	0.958	Probably Damaging	2.39	Pathogenic	0.00	Affected	3.77	5	0.3581	0.1343		-3	-3	-5.4	-16.04
c.2774T>C	L925P 2D AIThe SynGAP1 missense variant L925P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only ESM1b, whereas the remaining tools—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as likely pathogenic. Foldetta results are not available for this variant. Overall, the preponderance of evidence from multiple in silico predictors indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.483068	Structured	0.977963	Binding	0.290	0.852	0.125											-2.733	Likely Benign	0.985	Likely Pathogenic	Likely Pathogenic										0.501	Likely Pathogenic	-5.12	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.28	Pathogenic	0.00	Affected			0.3083	0.1996		-3	-3	-5.4	-16.04
c.2792T>C	L931P 2D AIThe SynGAP1 missense variant L931P is not reported in ClinVar and is absent from gnomAD. Prediction tools show a strong bias toward pathogenicity: SIFT, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, PROVEAN, and AlphaMissense‑Default all predict a deleterious effect, whereas only REVEL indicates a benign outcome. High‑accuracy assessments reinforce this trend: the SGM consensus—derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—classifies the variant as likely pathogenic, and AlphaMissense‑Optimized returns an uncertain result. Foldetta predictions are unavailable. Overall, the preponderance of evidence points to a pathogenic impact for L931P, and this conclusion is consistent with the absence of any ClinVar annotation, so there is no contradiction with existing clinical databases. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.549308	Disordered	0.989212	Binding	0.335	0.856	0.375											-8.624	Likely Pathogenic	0.950	Likely Pathogenic	Ambiguous										0.376	Likely Benign	-3.43	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.38	Pathogenic	0.01	Affected			0.3203	0.1698		-3	-3	-5.4	-16.04
c.2963T>C	L988P 2D AIThe SynGAP1 missense variant L988P is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 pathogenic vs. 2 benign). Foldetta results are unavailable. Overall, the majority of predictions (five pathogenic vs. four benign) lean toward pathogenicity. Thus, the variant is most likely pathogenic, and this conclusion does not contradict any existing ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.827927	Disordered	0.918781	Binding	0.360	0.913	0.750											-3.848	Likely Benign	0.703	Likely Pathogenic	Likely Benign										0.216	Likely Benign	-2.96	Deleterious	0.977	Probably Damaging	0.900	Possibly Damaging	2.62	Benign	0.00	Affected			0.3282	0.1698		-3	-3	-5.4	-16.04
c.3002T>C	L1001P 2D AIThe SynGAP1 missense variant L1001P is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) also indicates benign. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of evidence—including high‑accuracy tools—points to a benign effect, and this conclusion does not contradict the ClinVar “Uncertain” designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.754692	Disordered	0.958507	Binding	0.269	0.902	0.375					Uncertain		1				-3.071	Likely Benign	0.209	Likely Benign	Likely Benign										0.113	Likely Benign	-1.02	Neutral	0.966	Probably Damaging	0.690	Possibly Damaging	2.65	Benign	0.00	Affected	4.32	4	0.3322	0.0929		-3	-3	-5.4	-16.04
c.3065T>C	L1022P 2D AIThe SynGAP1 missense variant L1022P is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized, while pathogenic predictions arise from polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two pathogenic, two benign), and Foldetta data are unavailable. Overall, the balance of evidence favors a pathogenic interpretation, and this assessment does not conflict with ClinVar status because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.859585	Disordered	0.986981	Binding	0.339	0.752	0.500											-2.532	Likely Benign	0.643	Likely Pathogenic	Likely Benign										0.177	Likely Benign	-2.22	Neutral	0.995	Probably Damaging	0.925	Probably Damaging	2.49	Pathogenic	0.01	Affected			0.3332	0.1589		-3	-3	-5.4	-16.04
c.3071T>C	L1024P 2D AIThe SynGAP1 missense variant L1024P is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The SGM Consensus, which takes a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 benign vs 2 pathogenic). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of standard prediction tools lean toward pathogenicity, while high‑accuracy methods are inconclusive. Thus, the variant is most likely pathogenic based on the available predictions, and this assessment does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.862302	Disordered	0.992699	Binding	0.327	0.753	0.500											-4.385	Likely Benign	0.730	Likely Pathogenic	Likely Benign										0.149	Likely Benign	-2.42	Neutral	0.999	Probably Damaging	0.974	Probably Damaging	2.43	Pathogenic	0.03	Affected			0.3187	0.2033		-3	-3	-5.4	-16.04
c.3083T>C	L1028P 2D AIThe SynGAP1 missense variant L1028P is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Only AlphaMissense‑Default predicts a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; the Foldetta protein‑folding stability analysis is unavailable. Taken together, the majority of evidence points to a benign impact for this variant, and there is no ClinVar annotation to contradict this conclusion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.899122	Disordered	0.995137	Binding	0.364	0.730	0.500											-3.080	Likely Benign	0.594	Likely Pathogenic	Likely Benign										0.215	Likely Benign	-0.42	Neutral	0.004	Benign	0.010	Benign	2.70	Benign	0.25	Tolerated			0.2846	0.1763		-3	-3	-5.4	-16.04
c.3095T>C	L1032P 2D AIThe SynGAP1 missense variant L1032P has no ClinVar entry and is not reported in gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and the SGM‑Consensus score all classify the change as benign or likely benign. AlphaMissense‑Optimized also predicts a benign outcome, whereas SIFT uniquely flags the variant as pathogenic. The AlphaMissense‑Default assessment is uncertain, and no Foldetta stability data are available. High‑accuracy analyses reinforce the benign consensus: AlphaMissense‑Optimized reports a benign effect, and the SGM‑Consensus (derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates benign. Foldetta results are missing, so they do not influence the interpretation. Overall, the majority of computational evidence supports a benign classification, which is consistent with the absence of a ClinVar pathogenic annotation. Thus, the variant is most likely benign, and this conclusion does not contradict ClinVar status, as no ClinVar pathogenic claim exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.865454	Disordered	0.995318	Binding	0.365	0.735	0.500											-2.560	Likely Benign	0.449	Ambiguous	Likely Benign										0.142	Likely Benign	-0.71	Neutral	0.012	Benign	0.017	Benign	2.64	Benign	0.05	Affected			0.3024	0.2330		-3	-3	-5.4	-16.04
c.3272T>C	L1091P 2D AIThe SynGAP1 missense variant L1091P is listed in gnomAD (ID 6‑33443824‑T‑C) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, and ESM1b, while pathogenic predictions are reported by polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. AlphaMissense‑Optimized returns an uncertain result, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a 2‑vs‑2 tie, leaving it inconclusive. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of tools (five pathogenic vs three benign) predict a deleterious effect, and the high‑accuracy AlphaMissense‑Optimized score is uncertain. Consequently, the variant is most likely pathogenic based on current predictions, and this assessment does not contradict any ClinVar status, as none is reported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.924947	Disordered	0.984454	Binding	0.376	0.889	1.000								6-33443824-T-C			-4.139	Likely Benign	0.871	Likely Pathogenic	Ambiguous										0.180	Likely Benign	-1.25	Neutral	0.997	Probably Damaging	0.939	Probably Damaging	2.45	Pathogenic	0.04	Affected	3.77	5	0.3199	0.1918		-3	-3	-5.4	-16.04
c.3326T>C	L1109P 2D AIThe SynGAP1 missense variant L1109P is listed in ClinVar with an uncertain significance (ClinVar ID 1730257.0) and is not reported in gnomAD. Functional prediction tools uniformly classify the substitution as benign: REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all return benign scores. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized indicates a benign effect, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta, a protein‑folding stability predictor combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the computational evidence overwhelmingly supports a benign classification, which does not contradict the ClinVar uncertain status. Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.856457	Disordered	0.948334	Binding	0.343	0.893	0.875					Conflicting		2				-5.313	Likely Benign	0.120	Likely Benign	Likely Benign										0.151	Likely Benign	-0.52	Neutral	0.002	Benign	0.003	Benign	2.65	Benign	0.07	Tolerated	4.32	2	0.3159	0.2330		-3	-3	-5.4	-16.04
c.3386T>C	L1129P 2D AIThe SynGAP1 missense variant L1129P is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) also indicates benign. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of evidence—including high‑accuracy tools—points to a benign effect, and this conclusion does not contradict the current ClinVar “Uncertain” status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.903857	Disordered	0.876543	Binding	0.339	0.909	0.875					Uncertain		2				-2.991	Likely Benign	0.154	Likely Benign	Likely Benign										0.432	Likely Benign	0.27	Neutral	0.971	Probably Damaging	0.773	Possibly Damaging	5.44	Benign	0.00	Affected	4.32	4	0.3017	0.2231		-3	-3	-5.4	-16.04
c.3491T>C	L1164P 2D AIThe SynGAP1 missense variant L1164P has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic impact are REVEL, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic, SGM‑Consensus as Likely Benign, and Foldetta results are unavailable. Overall, the majority of tools (seven pathogenic vs. three benign) predict a deleterious effect, indicating that the variant is most likely pathogenic. This prediction does not contradict ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.517562	Disordered	0.853935	Binding	0.325	0.815	0.375											-3.928	Likely Benign	0.997	Likely Pathogenic	Likely Pathogenic										0.573	Likely Pathogenic	-2.16	Neutral	0.999	Probably Damaging	0.999	Probably Damaging	5.41	Benign	0.04	Affected			0.3173	0.1414		-3	-3	-5.4	-16.04
c.3539T>C	L1180P 2D AISynGAP1 missense variant L1180P is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic impact are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, whereas the SGM‑Consensus remains likely benign; Foldetta results are unavailable. Overall, the balance of evidence, including the consensus prediction and the higher number of benign calls, suggests the variant is most likely benign, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.626927	Disordered	0.559845	Binding	0.591	0.672	0.250											-4.564	Likely Benign	0.994	Likely Pathogenic	Likely Pathogenic										0.213	Likely Benign	-1.37	Neutral	0.992	Probably Damaging	0.930	Probably Damaging	2.65	Benign	0.00	Affected			0.3556	0.1155		-3	-3	-5.4	-16.04
c.3575T>C	L1192P 2D AIThe SynGAP1 missense variant L1192P is not reported in ClinVar and has no gnomAD entry. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which is a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, whereas the SGM‑Consensus remains benign; Foldetta results are unavailable. Overall, the balance of evidence leans toward a benign interpretation, and this assessment does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.575842	Disordered	0.441757	Uncertain	0.762	0.609	0.625											-4.610	Likely Benign	0.989	Likely Pathogenic	Likely Pathogenic										0.181	Likely Benign	-1.94	Neutral	0.997	Probably Damaging	0.959	Probably Damaging	2.65	Benign	0.05	Affected			0.3515	0.1053		-3	-3	-5.4	-16.04
c.3614T>C	L1205P 2D AIThe SynGAP1 missense variant L1205P is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. All available in silico predictors classify the change as pathogenic: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign effect. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized is pathogenic, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Pathogenic.” Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the computational evidence strongly indicates that the variant is pathogenic, which contradicts the current ClinVar designation of uncertainty. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.595080	Disordered	0.552471	Binding	0.880	0.576	0.375					Uncertain		1				-16.878	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic										0.536	Likely Pathogenic	-5.91	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.45	Pathogenic	0.00	Affected			0.3559	0.1053		-3	-3	-5.4	-16.04
c.3626T>C	L1209P 2D AIThe SynGAP1 missense variant L1209P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is also pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic and the SGM‑Consensus as pathogenic; Foldetta results are unavailable. Based on the overwhelming agreement among pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.595080	Disordered	0.583711	Binding	0.899	0.574	0.375											-17.259	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic										0.448	Likely Benign	-5.92	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.45	Pathogenic	0.00	Affected			0.3646	0.1053		-3	-3	-5.4	-16.04
c.3647T>C	L1216P 2D AIThe SynGAP1 missense variant L1216P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a deleterious effect: REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as pathogenic. No tool predicts a benign outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports the variant as likely pathogenic. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus confirms a likely pathogenic status. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of available predictions strongly suggests that the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.580690	Disordered	0.504713	Binding	0.863	0.563	0.250											-16.029	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic										0.524	Likely Pathogenic	-5.28	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.13	Pathogenic	0.00	Affected			0.3281	0.1048		-3	-3	-5.4	-16.04
c.3668T>C	L1223P 2D AIThe SynGAP1 missense variant L1223P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a deleterious effect: REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as pathogenic. No tool predicts a benign outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports the variant as Likely Pathogenic. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus agrees. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the concordant pathogenic predictions and the lack of benign evidence, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.608892	Disordered	0.436267	Uncertain	0.868	0.540	0.375											-14.728	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic										0.500	Likely Pathogenic	-5.17	Deleterious	1.000	Probably Damaging	0.990	Probably Damaging	1.45	Pathogenic	0.01	Affected			0.3413	0.2352		-3	-3	-5.4	-16.04
c.3671T>C	L1224P 2D AIThe SynGAP1 missense variant L1224P is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). In silico predictors that agree on a benign effect include REVEL and SIFT, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—consistently predict a pathogenic outcome. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is also likely pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of predictions indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by ClinVar status, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.525368	Disordered	0.441554	Uncertain	0.871	0.543	0.500											-11.727	Likely Pathogenic	0.981	Likely Pathogenic	Likely Pathogenic										0.149	Likely Benign	-3.18	Deleterious	0.998	Probably Damaging	0.948	Probably Damaging	2.36	Pathogenic	0.07	Tolerated			0.3618	0.1053		-3	-3	-5.4	-16.04
c.3701T>C	L1234P 2D AIThe SynGAP1 missense variant L1234P is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts Pathogenic, and the SGM‑Consensus confirms a Likely Pathogenic status. Foldetta results are unavailable, so they do not influence the overall assessment. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.599170	Disordered	0.575096	Binding	0.844	0.527	0.125											-14.931	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic										0.319	Likely Benign	-5.19	Deleterious	0.999	Probably Damaging	0.969	Probably Damaging	1.45	Pathogenic	0.01	Affected			0.3201	0.2483		-3	-3	-5.4	-16.04
c.3722T>C	L1241P 2D AIThe SynGAP1 missense variant L1241P is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM‑Consensus as Likely Pathogenic; Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.545602	Disordered	0.488880	Uncertain	0.828	0.541	0.375											-16.301	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic										0.471	Likely Benign	-5.42	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.61	Pathogenic	0.00	Affected			0.3640	0.1048		-3	-3	-5.4	-16.04
c.3743T>C	L1248P 2D AIThe SynGAP1 missense variant L1248P is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus agrees. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.834292	Disordered	0.371716	Uncertain	0.880	0.562	0.625											-14.647	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic										0.410	Likely Benign	-5.45	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.64	Pathogenic	0.00	Affected			0.3596	0.0848		-3	-3	-5.4	-16.04
c.3797T>C	L1266P 2D AIThe SynGAP1 missense variant L1266P is reported in gnomAD (6‑33447845‑T‑C) but has no ClinVar entry. Prediction tools cluster into two groups: benign predictions are made only by REVEL, whereas all other evaluated algorithms (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic effect. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized returns a pathogenic score, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates “Likely Pathogenic.” The Foldetta stability analysis is unavailable for this variant. Overall, the consensus of both general and high‑accuracy predictors points to a pathogenic impact, and this conclusion is not contradicted by any ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.433034	Structured	0.802655	Binding	0.868	0.602	0.000								6-33447845-T-C			-16.566	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic										0.424	Likely Benign	-5.83	Deleterious	0.999	Probably Damaging	0.977	Probably Damaging	2.10	Pathogenic	0.00	Affected	3.77	5	0.3150	0.2283		-3	-3	-5.4	-16.04
c.3803T>C	L1268P 2D AIThe SynGAP1 missense variant L1268P is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which takes a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 pathogenic vs. 2 benign). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of high‑accuracy predictors (5 vs. 4) indicate a pathogenic impact. This conclusion is not contradicted by ClinVar status, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.458154	Structured	0.804315	Binding	0.859	0.629	0.000											-9.062	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic										0.091	Likely Benign	-1.03	Neutral	0.970	Probably Damaging	0.637	Possibly Damaging	2.65	Benign	0.24	Tolerated			0.3261	0.1053		-3	-3	-5.4	-16.04
c.3818T>C	L1273P 2D AIThe SynGAP1 missense variant L1273P is not reported in ClinVar (ClinVar status: not listed) but is present in the gnomAD database (gnomAD ID: 6‑33447866‑T‑C). Functional prediction tools uniformly indicate a deleterious effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as pathogenic. No tool in the dataset predicts a benign outcome. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports the variant as likely pathogenic. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the consensus of predictive algorithms strongly supports a pathogenic classification, and this assessment does not contradict the ClinVar status, which simply lacks an entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.599170	Disordered	0.773625	Binding	0.747	0.677	0.500								6-33447866-T-C			-9.443	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic										0.523	Likely Pathogenic	-5.87	Deleterious	0.997	Probably Damaging	0.950	Probably Damaging	2.12	Pathogenic	0.00	Affected	3.77	5	0.3836	0.1343		-3	-3	-5.4	-16.04
c.3851T>C	L1284P 2D AIThe SynGAP1 missense variant L1284P is not reported in ClinVar (no ClinVar ID) but is present in gnomAD (ID 6‑33447899‑T‑C). Prediction tools that agree on a benign effect include REVEL, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive because it yields a 2‑to‑2 split. Foldetta results are unavailable. Overall, the balance of evidence slightly favors a pathogenic interpretation (five pathogenic versus four benign predictions). This assessment does not conflict with ClinVar, as the variant has no ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.812494	Disordered	0.824557	Binding	0.441	0.748	0.875								6-33447899-T-C			-2.451	Likely Benign	0.076	Likely Benign	Likely Benign										0.191	Likely Benign	-3.05	Deleterious	0.990	Probably Damaging	0.722	Possibly Damaging	2.48	Pathogenic	0.01	Affected	3.77	5	0.3307	0.0848		-3	-3	-5.4	-16.04
c.3872T>C	L1291P 2D AIThe SynGAP1 missense variant L1291P is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two benign vs two pathogenic votes). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, five tools predict pathogenicity while four predict benignity, giving a slight tilt toward a pathogenic interpretation. Because there is no ClinVar assertion, this prediction does not contradict any existing clinical classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.827927	Disordered	0.863458	Binding	0.579	0.797	0.625											-3.322	Likely Benign	0.243	Likely Benign	Likely Benign										0.417	Likely Benign	-4.32	Deleterious	0.990	Probably Damaging	0.856	Possibly Damaging	2.48	Pathogenic	0.01	Affected			0.3078	0.2162		-3	-3	-5.4	-16.04
c.3875T>C	L1292P 2D AISynGAP1 missense variant L1292P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Functional prediction tools cluster into two groups: benign predictions come from REVEL, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a 2‑to‑2 split and is therefore inconclusive. Foldetta, a protein‑folding stability method that combines FoldX‑MD and Rosetta outputs, has no available result for this variant. With half the tools indicating benign and half indicating pathogenic, the overall computational evidence is ambiguous. Consequently, the variant is neither clearly benign nor pathogenic based on current predictions, and there is no ClinVar entry to contradict this uncertainty. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.779859	Disordered	0.882643	Binding	0.586	0.800	0.625											-3.761	Likely Benign	0.264	Likely Benign	Likely Benign										0.311	Likely Benign	-4.58	Deleterious	0.971	Probably Damaging	0.773	Possibly Damaging	2.46	Pathogenic	0.01	Affected			0.3855	0.1220		-3	-3	-5.4	-16.04
c.3896T>C	L1299P 2D AIThe SynGAP1 missense variant L1299P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized, while pathogenic calls come from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. Grouping by consensus, the majority of predictors (five out of nine) favor a benign effect, and the SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely benign outcome. High‑accuracy assessments further support this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) is likely benign; Foldetta data are unavailable. Consequently, the variant is most likely benign according to the available computational evidence, and this assessment does not contradict any ClinVar annotation because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.771762	Disordered	0.896323	Binding	0.398	0.832	0.750											-2.589	Likely Benign	0.222	Likely Benign	Likely Benign										0.322	Likely Benign	-4.06	Deleterious	0.971	Probably Damaging	0.690	Possibly Damaging	2.67	Benign	0.01	Affected			0.3552	0.1309		-3	-3	-5.4	-16.04
c.3932T>C	L1311P 2D AIThe SynGAP1 missense variant L1311P is listed in ClinVar (ID 833866.0) as Benign and is present in gnomAD (variant ID 6‑33451806‑T‑C). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only polyPhen‑2 HumDiv predicts a pathogenic outcome. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a Likely Benign classification, and AlphaMissense‑Optimized also reports Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, is not available for this variant. Overall, the majority of computational evidence supports a benign effect, which is consistent with the ClinVar benign annotation and does not contradict the database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.816150	Disordered	0.968153	Binding	0.393	0.907	0.750					Likely Benign		1	6-33451806-T-C	1	6.21e-7	-1.831	Likely Benign	0.079	Likely Benign	Likely Benign										0.123	Likely Benign	-0.52	Neutral	0.579	Possibly Damaging	0.335	Benign	2.72	Benign	0.18	Tolerated	3.77	5	0.3181	0.1794		-3	-3	-5.4	-16.04
c.3953T>C	L1318P 2D AIThe SynGAP1 missense variant L1318P is listed in gnomAD (ID 6‑33451827‑T‑C) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and polyPhen‑2 HumVar, while pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments further support benignity: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) also indicates benign. Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for this variant, and this conclusion does not contradict any ClinVar status, as no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.887230	Disordered	0.968271	Binding	0.399	0.865	0.750								6-33451827-T-C			-2.307	Likely Benign	0.116	Likely Benign	Likely Benign										0.126	Likely Benign	-2.90	Deleterious	0.813	Possibly Damaging	0.212	Benign	3.98	Benign	0.00	Affected	3.77	5	0.3424	0.1411		-3	-3	-5.4	-16.04
c.3986T>C	L1329P 2D AIThe SynGAP1 missense variant L1329P is listed in gnomAD (ID 6‑33451860‑T‑C) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, ESM1b, and FATHMM, while pathogenic predictions are reported by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a tie and is therefore inconclusive. No Foldetta stability assessment is available. Overall, the majority of high‑confidence predictors (five pathogenic vs three benign) lean toward a pathogenic effect. Because ClinVar contains no classification, there is no conflict with existing clinical annotation. Thus, based on current in silico evidence, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.930790	Disordered	0.924905	Binding	0.336	0.748	0.875								6-33451860-T-C			-2.903	Likely Benign	0.951	Likely Pathogenic	Ambiguous										0.165	Likely Benign	-3.74	Deleterious	0.994	Probably Damaging	0.993	Probably Damaging	3.04	Benign	0.00	Affected	3.77	5	0.3396	0.1794		-3	-3	-5.4	-16.04
c.398T>C	L133P 2D AIThe SynGAP1 missense variant L133P is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect are REVEL and FATHMM, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. ESM1b remains uncertain. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default (pathogenic), ESM1b (uncertain), FATHMM (benign), and PROVEAN (pathogenic), yields a pathogenic consensus. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion does not contradict any existing ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.422041	Structured	0.718429	Binding	0.320	0.896	0.250											-7.744	In-Between	0.982	Likely Pathogenic	Likely Pathogenic										0.342	Likely Benign	-3.16	Deleterious	0.700	Possibly Damaging	0.483	Possibly Damaging	3.52	Benign	0.00	Affected			0.3270	0.1048		-3	-3	-5.4	-16.04
c.410T>C	L137P 2D AIThe SynGAP1 missense variant L137P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN)—all predict a pathogenic or likely pathogenic outcome. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus indicates it is likely pathogenic. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of computational evidence points to a pathogenic effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.553315	Disordered	0.639549	Binding	0.377	0.897	0.375											-11.067	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.377	Likely Benign	-3.77	Deleterious	0.998	Probably Damaging	0.995	Probably Damaging	3.59	Benign	0.00	Affected			0.3620	0.1177		-3	-3	-5.4	-16.04
c.449T>C	L150P 2D AIThe SynGAP1 missense variant L150P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN)—all predict a pathogenic or likely pathogenic outcome. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus indicates it is likely pathogenic. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of computational evidence points to a pathogenic effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.494003	Structured	0.505752	Binding	0.299	0.839	0.625											-12.881	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic										0.320	Likely Benign	-3.90	Deleterious	0.998	Probably Damaging	0.995	Probably Damaging	3.64	Benign	0.00	Affected			0.3557	0.1543		-3	-3	-5.4	-16.04
c.479T>C	L160P 2D AIThe SynGAP1 missense variant L160P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that predict a pathogenic effect comprise PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy consensus, SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a majority pathogenic vote (3 pathogenic vs. 1 benign) and is labeled “Likely Pathogenic.” AlphaMissense‑Optimized independently predicts pathogenicity. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the collective predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status, as none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.454136	Structured	0.526760	Binding	0.275	0.728	0.125											-15.939	Likely Pathogenic	0.969	Likely Pathogenic	Likely Pathogenic										0.283	Likely Benign	-3.06	Deleterious	0.001	Benign	0.000	Benign	3.86	Benign	0.00	Affected			0.3589	0.1484		-3	-3	-5.4	-16.04
c.518T>C	L173P 2D AIThe SynGAP1 missense variant L173P is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, and FATHMM, whereas tools that agree on a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized score is uncertain, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive because it yields a 2‑to‑2 split; Foldetta results are not available. Consequently, the computational evidence is evenly divided, providing no clear advantage for either benign or pathogenic classification. The variant is therefore most likely inconclusive based on current predictions, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.534167	Disordered	0.491566	Uncertain	0.390	0.631	0.375											-8.758	Likely Pathogenic	0.918	Likely Pathogenic	Ambiguous										0.135	Likely Benign	-2.38	Neutral	0.838	Possibly Damaging	0.466	Possibly Damaging	3.92	Benign	0.15	Tolerated			0.3318	0.1382		-3	-3	-5.4	-16.04
c.560T>C	L187P 2D AIThe SynGAP1 missense variant L187P is listed in gnomAD (ID 6‑33435202‑T‑C) but has no ClinVar entry. Functional prediction tools split in two groups: benign predictions come from REVEL and FATHMM, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all indicate pathogenicity. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus classifies the variant as Likely Pathogenic. No Foldetta stability result is available, so it does not influence the overall assessment. Based on the preponderance of pathogenic predictions, the variant is most likely pathogenic, and this conclusion is not contradicted by ClinVar status, which currently reports no classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.465241	Structured	0.428046	Uncertain	0.367	0.625	0.375								6-33435202-T-C	1	6.20e-7	-13.192	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic										0.320	Likely Benign	-5.17	Deleterious	0.917	Possibly Damaging	0.548	Possibly Damaging	3.70	Benign	0.01	Affected	3.47	9	0.3604	0.1484		-3	-3	-5.4	-16.04
c.593T>C	L198P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L198P has no ClinVar entry and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, Rosetta, and FATHMM, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; FoldX, Foldetta, and premPS are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Pathogenic, and Foldetta as uncertain. Overall, the majority of evidence points toward a deleterious effect. Thus, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.444081	Structured	0.431715	Uncertain	0.572	0.485	0.125											-12.250	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	1.55	Ambiguous	0.3	0.40	Likely Benign	0.98	Ambiguous	0.65	Ambiguous	0.491	Likely Benign	-5.87	Deleterious	0.997	Probably Damaging	0.916	Probably Damaging	3.33	Benign	0.00	Affected			0.3882	0.1582		-3	-3	-5.4	-16.04
c.641T>C	L214P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L214P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only FATHMM, while the remaining 15 tools (REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, SGM‑Consensus, and the consensus of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) uniformly predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized scores the variant as pathogenic; the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely pathogenic outcome; and Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, also classifies the variant as pathogenic. Based on the overwhelming agreement among predictive algorithms, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.155435	Structured	0.372604	Uncertain	0.818	0.302	0.125											-11.348	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	3.38	Destabilizing	1.3	7.51	Destabilizing	5.45	Destabilizing	1.30	Destabilizing	0.930	Likely Pathogenic	-5.98	Deleterious	0.997	Probably Damaging	0.916	Probably Damaging	5.76	Benign	0.00	Affected			0.3448	0.1553		-3	-3	-5.4	-16.04
c.737T>C	L246P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L246P is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: the single benign prediction comes from FATHMM, while all other evaluated algorithms (SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) uniformly predict a pathogenic effect. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized indicates pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is labeled Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenicity. No prediction or folding stability result is missing or inconclusive. Based on the consensus of these tools, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.472492	Structured	0.302312	Uncertain	0.859	0.364	0.000											-16.581	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	6.42	Destabilizing	0.3	8.72	Destabilizing	7.57	Destabilizing	1.79	Destabilizing	0.944	Likely Pathogenic	-6.30	Deleterious	0.997	Probably Damaging	0.916	Probably Damaging	4.67	Benign	0.00	Affected			0.3731	0.1582		-3	-3	-5.4	-16.04
c.791T>C	L264P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L264P is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that assess pathogenicity all converge on a deleterious effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity. No tool in the dataset reports a benign outcome. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, is pathogenic. Based on the unanimous computational evidence, the variant is most likely pathogenic, a conclusion that contradicts the current ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.185198	Structured	0.323473	Uncertain	0.939	0.264	0.000					Uncertain		1				-12.285	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	5.73	Destabilizing	0.3	6.57	Destabilizing	6.15	Destabilizing	2.65	Destabilizing	0.767	Likely Pathogenic	-6.43	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	0.49	Pathogenic	0.00	Affected			0.3239	0.1053		-3	-3	-5.4	-16.04
c.797T>C	L266P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L266P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a deleterious effect. Benign predictions: none. Pathogenic predictions: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts pathogenic. No conflicting benign evidence is present. Therefore, the variant is most likely pathogenic, and this conclusion is consistent with the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.232838	Structured	0.297157	Uncertain	0.948	0.264	0.000											-15.752	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	7.08	Destabilizing	0.1	4.02	Destabilizing	5.55	Destabilizing	2.31	Destabilizing	0.654	Likely Pathogenic	-6.06	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.53	Pathogenic	0.00	Affected			0.3158	0.1021		-3	-3	-5.4	-16.04
c.821T>C	L274P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L274P is not reported in ClinVar (ClinVar status: not listed) and is absent from gnomAD (no gnomAD ID). Prediction tools that assess pathogenicity uniformly classify the variant as deleterious: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a pathogenic effect. No tool in the dataset predicts a benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized indicates pathogenicity; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also reports Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, predicts a pathogenic impact. Based on the unanimous computational evidence, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.066181	Structured	0.377483	Uncertain	0.866	0.195	0.250											-14.667	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	5.62	Destabilizing	1.5	4.49	Destabilizing	5.06	Destabilizing	1.66	Destabilizing	0.804	Likely Pathogenic	-6.30	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	0.00	Pathogenic	0.00	Affected			0.3535	0.0625		-3	-3	-5.4	-16.04
c.851T>C	L284P 2D AIThe SynGAP1 missense variant L284P is listed in ClinVar as Pathogenic (ClinVar ID 3344808.0) and is not reported in gnomAD. Prediction tools that assess functional impact uniformly classify the variant as pathogenic: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign effect. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts pathogenic. Based on the unanimous computational evidence, the variant is most likely pathogenic, and this conclusion aligns with its ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.094817	Structured	0.371601	Uncertain	0.950	0.255	0.000					Likely Pathogenic		1				-15.588	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	5.83	Destabilizing	0.2	5.81	Destabilizing	5.82	Destabilizing	1.89	Destabilizing	0.794	Likely Pathogenic	-6.17	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.64	Pathogenic	0.00	Affected			0.3540	0.1021		-3	-3	-5.4	-16.04
c.857T>C	L286P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L286P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a deleterious effect. Benign predictions: none. Pathogenic predictions: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. Based on the consensus of all available predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.122885	Structured	0.385647	Uncertain	0.932	0.260	0.000											-14.982	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	5.43	Destabilizing	0.9	6.38	Destabilizing	5.91	Destabilizing	2.10	Destabilizing	0.878	Likely Pathogenic	-6.43	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.47	Pathogenic	0.00	Affected			0.3719	0.1182		-3	-3	-5.4	-16.04
c.869T>C	L290P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L290P is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess pathogenicity unanimously favor a deleterious effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all predict pathogenicity. No tool in the dataset predicts a benign outcome; the remaining tools (FoldX, Rosetta, Foldetta, premPS) return uncertain results, which are treated as unavailable evidence. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is pathogenic, SGM‑Consensus is likely pathogenic, and Foldetta is inconclusive. Based on the collective predictions, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.127496	Structured	0.399723	Uncertain	0.904	0.255	0.000											-11.796	Likely Pathogenic	0.973	Likely Pathogenic	Likely Pathogenic	0.79	Ambiguous	0.1	1.10	Ambiguous	0.95	Ambiguous	0.56	Ambiguous	0.727	Likely Pathogenic	-6.43	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.01	Pathogenic	0.03	Affected			0.3646	0.1703		-3	-3	-5.4	-16.04
c.950T>C	L317P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L317P is not reported in ClinVar (ClinVar status: not listed) and is absent from gnomAD (gnomAD ID: none). Prediction tools that assess pathogenicity unanimously classify the variant as deleterious: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tools predict a benign effect, so the benign group is empty. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts Pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts Pathogenic. Based on the collective predictions, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because the variant is not yet reported there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.106997	Structured	0.394031	Uncertain	0.874	0.240	0.125											-14.778	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	3.61	Destabilizing	1.4	4.29	Destabilizing	3.95	Destabilizing	1.26	Destabilizing	0.654	Likely Pathogenic	-6.43	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.82	Pathogenic	0.00	Affected			0.3405	0.1153		-3	-3	-5.4	-16.04
c.968T>C	L323P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L323P is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that assess pathogenicity uniformly indicate a deleterious effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as pathogenic. No tool in the dataset predicts a benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, is pathogenic. Based on the unanimous computational evidence, the variant is most likely pathogenic, a conclusion that contradicts the current ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.268042	Structured	0.428564	Uncertain	0.956	0.369	0.000					Uncertain		2				-12.507	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	3.39	Destabilizing	0.6	8.46	Destabilizing	5.93	Destabilizing	2.20	Destabilizing	0.762	Likely Pathogenic	-4.80	Deleterious	0.999	Probably Damaging	0.977	Probably Damaging	0.59	Pathogenic	0.01	Affected	4.29	398	0.3678	0.1221		-3	-3	-5.4	-16.04	201.9	68.2	0.0	0.1	0.6	0.3	X							Potentially Pathogenic	The iso-butyl side chain of Leu323, located at the beginning of an anti-parallel β sheet strand (res. Ala322-Asp330), packs against multiple hydrophobic leucine residues (e.g., Leu264, Leu266, Leu284, Leu286). In contrast, in the variant simulations, the less bulky cyclic five-membered pyrrolidine ring of Pro323 cannot fill the hydrophobic space as effectively as the branched hydrocarbon side chain of leucine. Notably, the backbone amide group of Leu323 forms a hydrogen bond with the backbone carbonyl group of Cys285. Pro323 cannot form this bond due to the absence of the backbone amide group, resulting in partial unfolding of the anti-parallel β sheet end in the variant simulations.
c.974T>C	L325P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L325P is not reported in ClinVar (ClinVar status: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that assess pathogenicity all agree on a deleterious effect: SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as pathogenic. No tool predicts a benign outcome. High‑accuracy methods reinforce this consensus: AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates pathogenicity; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, reports a pathogenic effect. No predictions or stability results are missing or inconclusive. Based on the unanimous computational evidence, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.352862	Structured	0.424577	Uncertain	0.955	0.436	0.000											-16.130	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	5.49	Destabilizing	0.3	7.27	Destabilizing	6.38	Destabilizing	1.89	Destabilizing	0.607	Likely Pathogenic	-4.37	Deleterious	0.999	Probably Damaging	0.977	Probably Damaging	1.33	Pathogenic	0.00	Affected			0.3393	0.1903		-3	-3	-5.4	-16.04
c.980T>C	L327P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L327P (ClinVar ID 660421) is classified as Pathogenic in ClinVar and is not reported in gnomAD. Prediction tools that assess functional impact uniformly indicate a deleterious effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity, leaving no tools in the benign category. High‑accuracy assessments further support this: AlphaMissense‑Optimized is Pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is Pathogenic. Based on the unanimous computational evidence, the variant is most likely pathogenic, and this conclusion aligns with its ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.335645	Structured	0.409189	Uncertain	0.939	0.490	0.000					Pathogenic/Likely path.		4				-16.602	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	5.38	Destabilizing	0.1	4.00	Destabilizing	4.69	Destabilizing	2.62	Destabilizing	0.658	Likely Pathogenic	-5.97	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.52	Pathogenic	0.01	Affected	3.38	23	0.3921	0.1703		-3	-3	-5.4	-16.04	221.7	69.4	0.1	0.0	0.6	0.1	X							Potentially Pathogenic	The backbone amide group of Leu327, located in the middle of an anti-parallel β sheet strand (res. Ala322-Asp330), forms a hydrogen bond with the carbonyl group of Gly344 on a neighboring β strand (res. Lys336-Pro349) in the WT simulations. In contrast, in the variant simulations, the introduction of Pro327 destabilizes the hydrogen bonding between the two anti-parallel β strands because proline lacks the backbone amide group altogether. Additionally, in the WT simulations, the iso-butyl side chain of Leu327 packs against multiple hydrophobic residues (e.g., Leu274, V400, Val343), whereas the less bulky cyclic five-membered pyrrolidine ring of Pro327 cannot fill the same space as effectively. Thus, although no large-scale unfolding is observed during the variant simulations, the residue swap is likely to cause severe problems for the correct C2 domain folding, which could also affect the SynGAP-membrane association.	10.1016/j.ajhg.2020.11.011
c.101A>T	Y34F 2D AIThe SynGAP1 missense variant Y34F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign; no Foldetta stability result is available. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.529623	Disordered	0.435847	Uncertain	0.303	0.855	0.375											-3.275	Likely Benign	0.127	Likely Benign	Likely Benign										0.094	Likely Benign	-0.50	Neutral	0.458	Possibly Damaging	0.481	Possibly Damaging	4.20	Benign	0.00	Affected			0.2604	0.3591		7	3	4.1	-16.00
c.1025A>T	Y342F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y342F is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive and therefore treated as unavailable. Overall, the majority of evidence points to a benign impact. This conclusion does not contradict the ClinVar status, which currently has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.366687	Structured	0.408200	Uncertain	0.866	0.487	0.250											-6.987	Likely Benign	0.145	Likely Benign	Likely Benign	-0.13	Likely Benign	0.1	0.42	Likely Benign	0.15	Likely Benign	0.05	Likely Benign	0.160	Likely Benign	-2.67	Deleterious	0.999	Probably Damaging	0.992	Probably Damaging	2.03	Pathogenic	0.26	Tolerated			0.2626	0.3615		7	3	4.1	-16.00
c.1088A>T	Y363F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y363F is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM; premPS is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑vs‑2 split. Overall, seven tools predict benign while four predict pathogenic, with no evidence of pathogenicity from the most accurate methods. Therefore, the variant is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.321458	Structured	0.435392	Uncertain	0.954	0.586	0.125											-6.621	Likely Benign	0.114	Likely Benign	Likely Benign	-0.23	Likely Benign	0.0	0.42	Likely Benign	0.10	Likely Benign	0.58	Ambiguous	0.293	Likely Benign	-3.42	Deleterious	0.997	Probably Damaging	0.970	Probably Damaging	1.74	Pathogenic	0.18	Tolerated			0.2781	0.3583		7	3	4.1	-16.00
c.109T>G	S37A 2D AIThe SynGAP1 missense variant S37A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The high‑accuracy consensus, SGM‑Consensus, classifies the variant as Likely Benign, and AlphaMissense‑Optimized also reports a benign prediction. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation; there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.642678	Disordered	0.433492	Uncertain	0.317	0.806	0.500											-4.052	Likely Benign	0.125	Likely Benign	Likely Benign										0.045	Likely Benign	-0.86	Neutral	0.140	Benign	0.355	Benign	3.98	Benign	0.00	Affected			0.5089	0.4970	Weaken	1	1	2.6	-16.00
c.10T>G	S4A 2D AIThe SynGAP1 missense variant S4A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for S4A, and this conclusion does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.608892	Disordered	0.547364	Binding	0.390	0.924	0.750											-4.245	Likely Benign	0.111	Likely Benign	Likely Benign										0.050	Likely Benign	0.02	Neutral	0.140	Benign	0.097	Benign	4.22	Benign	0.00	Affected			0.4871	0.5755		1	1	2.6	-16.00
c.1120T>G	S374A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S374A is reported in gnomAD (6‑33438025‑T‑G) and has no ClinVar entry. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments—AlphaMissense‑Optimized, SGM‑Consensus, and Foldetta (combining FoldX‑MD and Rosetta outputs)—all indicate a benign effect. Based on the collective predictions, the variant is most likely benign, and this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.642678	Disordered	0.428948	Uncertain	0.333	0.812	0.625								6-33438025-T-G			-4.245	Likely Benign	0.082	Likely Benign	Likely Benign	-0.08	Likely Benign	0.1	0.41	Likely Benign	0.17	Likely Benign	0.10	Likely Benign	0.122	Likely Benign	-0.53	Neutral	0.012	Benign	0.011	Benign	5.32	Benign	0.04	Affected	4.32	13	0.5091	0.5774	Strenghten	1	1	2.6	-16.00
c.1135T>G	S379A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S379A is reported in gnomAD (variant ID 6‑33438040‑T‑G) but has no entry in ClinVar. All available in‑silico predictors classify the change as benign: REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the consensus SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). No tool predicts pathogenicity. High‑accuracy assessments are consistent: AlphaMissense‑Optimized predicts benign; the SGM‑Consensus (majority vote) indicates “Likely Benign”; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts benign. Consequently, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.728858	Disordered	0.433206	Uncertain	0.327	0.931	0.625								6-33438040-T-G			-4.300	Likely Benign	0.077	Likely Benign	Likely Benign	-0.22	Likely Benign	0.3	1.03	Ambiguous	0.41	Likely Benign	0.10	Likely Benign	0.217	Likely Benign	-0.50	Neutral	0.012	Benign	0.002	Benign	3.91	Benign	0.21	Tolerated	4.32	11	0.5032	0.5555	Strenghten	1	1	2.6	-16.00
c.1153T>G	S385A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S385A is catalogued in gnomAD (variant ID 6‑33438058‑T‑G) but has no entry in ClinVar. All available in silico predictors report a benign effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts pathogenicity. High‑accuracy assessments concur: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Benign”; and Foldetta (combining FoldX‑MD and Rosetta outputs) is benign. Consequently, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.733139	Disordered	0.425480	Uncertain	0.341	0.925	0.750								6-33438058-T-G			-4.412	Likely Benign	0.083	Likely Benign	Likely Benign	0.03	Likely Benign	0.1	0.19	Likely Benign	0.11	Likely Benign	0.07	Likely Benign	0.243	Likely Benign	-0.28	Neutral	0.140	Benign	0.355	Benign	4.65	Benign	0.13	Tolerated	4.32	3	0.4910	0.5366		1	1	2.6	-16.00
c.1165T>G	S389A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S389A is reported in gnomAD (ID 6‑33438070‑T‑G) and has no ClinVar entry. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is Benign; the SGM‑Consensus is Likely Benign; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also reports Benign. Overall, the preponderance of evidence indicates the variant is most likely benign, and this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.703578	Disordered	0.417444	Uncertain	0.306	0.803	0.875								6-33438070-T-G			-4.199	Likely Benign	0.081	Likely Benign	Likely Benign	0.01	Likely Benign	0.0	0.37	Likely Benign	0.19	Likely Benign	0.03	Likely Benign	0.326	Likely Benign	-0.39	Neutral	0.140	Benign	0.355	Benign	5.08	Benign	0.04	Affected	4.32	8	0.5037	0.5963	Strenghten	1	1	2.6	-16.00
c.116A>T	Y39F 2D AIThe SynGAP1 missense variant Y39F is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability analysis is available for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.425610	Structured	0.432876	Uncertain	0.343	0.787	0.375											-3.410	Likely Benign	0.119	Likely Benign	Likely Benign										0.073	Likely Benign	-0.78	Neutral	0.458	Possibly Damaging	0.481	Possibly Damaging	4.05	Benign	0.00	Affected			0.2641	0.3363		7	3	4.1	-16.00
c.1217A>T	Y406F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y406F is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: REVEL, FoldX, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all classify the variant as benign or likely benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, the SGM‑Consensus (majority vote) indicates likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts benign. Based on the collective evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.179055	Structured	0.393707	Uncertain	0.946	0.291	0.000											-3.427	Likely Benign	0.080	Likely Benign	Likely Benign	-0.01	Likely Benign	0.2	0.40	Likely Benign	0.20	Likely Benign	0.15	Likely Benign	0.079	Likely Benign	-0.93	Neutral	0.002	Benign	0.002	Benign	3.96	Benign	0.31	Tolerated			0.2673	0.3952		7	3	4.1	-16.00
c.1250A>T	Y417F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 Y417F variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, SIFT, and FATHMM. Those that predict a pathogenic impact are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Uncertain results come from AlphaMissense‑Optimized and premPS. High‑accuracy assessments show SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, Foldetta (combining FoldX‑MD and Rosetta) as Benign, and AlphaMissense‑Optimized as Uncertain. Overall, the majority of tools and the SGM‑Consensus score suggest a pathogenic effect, while Foldetta indicates a benign effect; the variant’s status is not contradicted by ClinVar (no entry). Thus, based on the available predictions, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.179055	Structured	0.346865	Uncertain	0.958	0.250	0.000											-11.368	Likely Pathogenic	0.852	Likely Pathogenic	Ambiguous	0.47	Likely Benign	0.1	-0.09	Likely Benign	0.19	Likely Benign	0.97	Ambiguous	0.367	Likely Benign	-3.82	Deleterious	0.999	Probably Damaging	0.985	Probably Damaging	3.03	Benign	0.06	Tolerated			0.2617	0.3098		7	3	4.1	-16.00
c.1268A>T	Y423F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y423F is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess sequence conservation and functional impact uniformly classify the substitution as benign: REVEL, FoldX, Rosetta, Foldetta, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Only two tools, polyPhen‑2 HumDiv and HumVar, predict a pathogenic effect, while premPS is inconclusive. High‑accuracy methods give consistent benign results: AlphaMissense‑Optimized is benign, the SGM‑Consensus is Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta) predicts benign stability. Overall, the overwhelming majority of evidence supports a benign effect, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.088832	Structured	0.421885	Uncertain	0.975	0.242	0.000											-5.533	Likely Benign	0.181	Likely Benign	Likely Benign	0.03	Likely Benign	0.1	-0.05	Likely Benign	-0.01	Likely Benign	0.76	Ambiguous	0.149	Likely Benign	-2.30	Neutral	0.999	Probably Damaging	0.985	Probably Damaging	3.45	Benign	0.60	Tolerated			0.1934	0.2337		7	3	4.1	-16.00
c.1283A>T	Y428F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y428F is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized, whereas a majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b) predict a pathogenic impact. Uncertain or inconclusive results are reported for FoldX, Rosetta, Foldetta, premPS, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta as unavailable. Overall, the balance of evidence—five pathogenic versus three benign predictions, with a pathogenic SGM Consensus and a benign AlphaMissense‑Optimized—suggests that the variant is most likely pathogenic. This conclusion is not contradicted by ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.118441	Structured	0.389652	Uncertain	0.965	0.292	0.000											-10.464	Likely Pathogenic	0.530	Ambiguous	Likely Benign	0.82	Ambiguous	0.1	0.52	Ambiguous	0.67	Ambiguous	0.89	Ambiguous	0.366	Likely Benign	-3.82	Deleterious	0.999	Probably Damaging	0.985	Probably Damaging	3.41	Benign	0.04	Affected			0.2719	0.3146		7	3	4.1	-16.00
c.1396T>G	S466A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S466A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: pathogenic scores are given by REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM, whereas benign predictions come from SIFT, PROVEAN, premPS, ESM1b, Rosetta, Foldetta, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, the SGM‑Consensus itself is Benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) also reports Benign. FoldX alone is Uncertain, but this does not alter the overall consensus. Taken together, the majority of evidence indicates the variant is most likely benign, and this conclusion is consistent with the absence of a ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.311707	Structured	0.322353	Uncertain	0.933	0.227	0.000											-6.928	Likely Benign	0.228	Likely Benign	Likely Benign	-0.50	Ambiguous	0.1	0.06	Likely Benign	-0.22	Likely Benign	0.37	Likely Benign	0.537	Likely Pathogenic	-1.46	Neutral	0.909	Possibly Damaging	0.987	Probably Damaging	-1.51	Pathogenic	0.10	Tolerated			0.4245	0.3996		1	1	2.6	-16.00
c.1411T>G	S471A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S471A is not reported in ClinVar and is absent from gnomAD. Across the spectrum of in‑silico predictors, the majority (REVEL, FoldX, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) classify the change as benign, whereas only FATHMM predicts it as pathogenic; Rosetta is inconclusive. High‑accuracy assessments reinforce the benign interpretation: AlphaMissense‑Optimized scores benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign stability. No evidence suggests pathogenicity, and the predictions do not contradict the absence of ClinVar annotation. Therefore, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.305330	Structured	0.355411	Uncertain	0.888	0.261	0.000											-5.516	Likely Benign	0.077	Likely Benign	Likely Benign	0.11	Likely Benign	0.1	-0.61	Ambiguous	-0.25	Likely Benign	0.23	Likely Benign	0.252	Likely Benign	-1.93	Neutral	0.010	Benign	0.037	Benign	-1.22	Pathogenic	0.29	Tolerated			0.4439	0.3691		1	1	2.6	-16.00
c.1490A>T	Y497F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y497F is not reported in ClinVar (ClinVar status: not listed) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include FoldX, Rosetta, Foldetta, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SGM‑Consensus, REVEL, PROVEAN, ESM1b, and FATHMM; premPS remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of predictions lean toward a benign impact, and this conclusion does not contradict the absence of a ClinVar classification. Thus, the variant is most likely benign based on the current predictive evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.092881	Structured	0.393608	Uncertain	0.950	0.181	0.000											-8.566	Likely Pathogenic	0.199	Likely Benign	Likely Benign	-0.27	Likely Benign	0.1	0.47	Likely Benign	0.10	Likely Benign	0.61	Ambiguous	0.578	Likely Pathogenic	-3.75	Deleterious	0.367	Benign	0.131	Benign	-1.15	Pathogenic	0.19	Tolerated			0.2074	0.2242		7	3	4.1	-16.00
c.1514A>T	Y505F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y505F is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, FoldX, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. Predictions that are uncertain or inconclusive are Rosetta, Foldetta, premPS, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of tools (five benign versus four pathogenic) lean toward a benign interpretation, and this is consistent with the lack of ClinVar evidence; thus the variant is most likely benign and does not contradict ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.047319	Structured	0.292227	Uncertain	0.909	0.188	0.000											-8.855	Likely Pathogenic	0.437	Ambiguous	Likely Benign	0.40	Likely Benign	0.0	0.76	Ambiguous	0.58	Ambiguous	0.69	Ambiguous	0.434	Likely Benign	-3.98	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	2.93	Benign	0.07	Tolerated			0.2409	0.2598		7	3	4.1	-16.00
c.154T>G	S52A 2D AIThe SynGAP1 missense variant S52A is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; the only tool predicting a pathogenic outcome is SIFT. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign classification. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise predicts benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of available predictions strongly supports a benign impact, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.291804	Structured	0.457753	Uncertain	0.499	0.677	0.000											-5.326	Likely Benign	0.196	Likely Benign	Likely Benign										0.040	Likely Benign	-0.69	Neutral	0.140	Benign	0.355	Benign	4.17	Benign	0.00	Affected			0.5389	0.5073	Strenghten	1	1	2.6	-16.00
c.1553A>T	Y518F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 Y518F missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, SIFT, FATHMM, AlphaMissense‑Optimized, and Foldetta. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. Two tools are uncertain: Rosetta and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic. Overall, the majority of individual predictors (seven benign vs. four pathogenic) support a benign classification, and this does not contradict the ClinVar status, which has no entry for this variant. Thus, based on the available predictions, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.139895	Structured	0.126970	Uncertain	0.897	0.321	0.000											-10.617	Likely Pathogenic	0.466	Ambiguous	Likely Benign	0.34	Likely Benign	0.1	-0.61	Ambiguous	-0.14	Likely Benign	0.41	Likely Benign	0.318	Likely Benign	-3.68	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	3.50	Benign	0.22	Tolerated			0.2107	0.2230		7	3	4.1	-16.00
c.1558T>G	S520A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 S520A missense variant is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized, whereas a larger group—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—consistently predict pathogenicity. The premPS score is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic. Overall, the majority of tools lean toward pathogenicity, and the high‑accuracy consensus is split, but the pathogenic predictions dominate. Thus, the variant is most likely pathogenic based on the available predictions, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.094817	Structured	0.084894	Uncertain	0.887	0.337	0.000											-8.417	Likely Pathogenic	0.704	Likely Pathogenic	Likely Benign	0.03	Likely Benign	0.2	0.19	Likely Benign	0.11	Likely Benign	0.56	Ambiguous	0.523	Likely Pathogenic	-2.55	Deleterious	0.944	Possibly Damaging	0.987	Probably Damaging	-1.31	Pathogenic	0.01	Affected			0.4887	0.3636		1	1	2.6	-16.00
c.1600T>G	S534A 2D 3DClick to see structure in 3D Viewer AISynGAP1 S534A is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate benign. Only two tools, polyPhen‑2 HumDiv and HumVar, predict pathogenicity. High‑accuracy methods reinforce the benign consensus: AlphaMissense‑Optimized scores benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign stability. No evidence suggests a deleterious effect. Therefore, the variant is most likely benign, and this assessment does not contradict any ClinVar annotation (none available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.167087	Structured	0.032173	Uncertain	0.860	0.362	0.000											-4.691	Likely Benign	0.082	Likely Benign	Likely Benign	0.01	Likely Benign	0.0	-0.01	Likely Benign	0.00	Likely Benign	0.11	Likely Benign	0.163	Likely Benign	-1.70	Neutral	0.880	Possibly Damaging	0.994	Probably Damaging	3.36	Benign	0.42	Tolerated			0.5042	0.3131	Weaken	1	1	2.6	-16.00
c.1669T>G	S557A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S557A is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include AlphaMissense‑Optimized and Rosetta, whereas a majority of tools (REVEL, SIFT, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and the SGM‑Consensus) predict a pathogenic impact. Uncertain or inconclusive results come from AlphaMissense‑Default, FoldX, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the preponderance of evidence points to a pathogenic effect. This conclusion is not contradicted by ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.028107	Structured	0.010261	Uncertain	0.924	0.215	0.000											-11.044	Likely Pathogenic	0.421	Ambiguous	Likely Benign	1.26	Ambiguous	0.0	0.09	Likely Benign	0.68	Ambiguous	0.54	Ambiguous	0.801	Likely Pathogenic	-2.70	Deleterious	0.944	Possibly Damaging	0.987	Probably Damaging	-1.69	Pathogenic	0.05	Affected			0.4695	0.4836		1	1	2.6	-16.00
c.1711T>G	S571A 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant S571A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that agree on a benign effect include FoldX, Rosetta, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), and FATHMM. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive because it yields a 2‑2 split. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta (combining FoldX‑MD and Rosetta outputs) as benign, and the SGM Consensus remains unavailable. Overall, the preponderance of evidence points to a benign impact for S571A, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.069024	Structured	0.045569	Uncertain	0.928	0.270	0.000											-6.344	Likely Benign	0.233	Likely Benign	Likely Benign	-0.44	Likely Benign	0.1	-0.19	Likely Benign	-0.32	Likely Benign	0.51	Ambiguous	0.563	Likely Pathogenic	-2.69	Deleterious	0.980	Probably Damaging	0.994	Probably Damaging	-1.22	Pathogenic	0.09	Tolerated			0.4739	0.2671		1	1	2.6	-16.00
c.1774T>G	S592A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S592A is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include FoldX, SIFT, and AlphaMissense‑Optimized, whereas a majority (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default) predict a pathogenic outcome. Tools with uncertain or inconclusive results are Rosetta, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the balance of evidence favors a pathogenic classification. This conclusion is not contradicted by ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.012270	Structured	0.100070	Uncertain	0.913	0.182	0.000											-10.902	Likely Pathogenic	0.572	Likely Pathogenic	Likely Benign	-0.48	Likely Benign	0.1	-0.93	Ambiguous	-0.71	Ambiguous	0.79	Ambiguous	0.661	Likely Pathogenic	-2.72	Deleterious	0.980	Probably Damaging	0.994	Probably Damaging	-1.25	Pathogenic	0.44	Tolerated			0.4878	0.3318		1	1	2.6	-16.00
c.1810T>G	S604A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S604A has no ClinVar record and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, SIFT, FATHMM, AlphaMissense‑Optimized, and Foldetta. Those that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Rosetta is uncertain and does not contribute to a consensus. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. With two of the three high‑accuracy tools indicating benign and no ClinVar evidence to contradict, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.010926	Structured	0.192527	Uncertain	0.911	0.195	0.000											-10.017	Likely Pathogenic	0.608	Likely Pathogenic	Likely Benign	0.02	Likely Benign	0.1	-0.60	Ambiguous	-0.29	Likely Benign	0.11	Likely Benign	0.378	Likely Benign	-2.99	Deleterious	0.944	Possibly Damaging	0.987	Probably Damaging	3.25	Benign	0.08	Tolerated			0.5198	0.3530	Weaken	1	1	2.6	-16.00
c.1841A>T	Y614F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y614F is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. Uncertain or unavailable results come from Foldetta, premPS, and Rosetta. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic), and Foldetta is unavailable. Overall, the majority of reliable predictors indicate a benign impact, and this conclusion does not contradict the lack of ClinVar annotation. Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.314870	Structured	0.182134	Uncertain	0.852	0.254	0.000											-5.584	Likely Benign	0.630	Likely Pathogenic	Likely Benign	0.09	Likely Benign	0.2	0.98	Ambiguous	0.54	Ambiguous	0.78	Ambiguous	0.364	Likely Benign	-3.75	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.42	Benign	0.07	Tolerated			0.1909	0.2762		7	3	4.1	-16.00
c.1858T>G	S620A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S620A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, FoldX, premPS, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as likely benign. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus as benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. No evidence from these analyses suggests a deleterious effect. Consequently, the variant is most likely benign based on the aggregate predictions, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.139895	Structured	0.100377	Uncertain	0.936	0.219	0.000											-4.637	Likely Benign	0.088	Likely Benign	Likely Benign	-0.42	Likely Benign	0.0	-0.90	Ambiguous	-0.66	Ambiguous	-0.19	Likely Benign	0.375	Likely Benign	-0.52	Neutral	0.968	Probably Damaging	0.994	Probably Damaging	-1.27	Pathogenic	0.66	Tolerated			0.4950	0.3636		1	1	2.6	-16.00
c.1909T>G	S637A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S637A is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include AlphaMissense‑Default, AlphaMissense‑Optimized, ESM1b, FATHMM, PROVEAN, SIFT, polyPhen‑2 (HumDiv and HumVar), REVEL, FoldX, and premPS. No tool predicts a pathogenic outcome. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Benign,” and Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, is inconclusive (Uncertain). Taken together, the overwhelming majority of evidence indicates a benign effect. The variant’s status is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.076542	Structured	0.083482	Uncertain	0.920	0.253	0.000											-4.186	Likely Benign	0.137	Likely Benign	Likely Benign	0.31	Likely Benign	0.1	0.99	Ambiguous	0.65	Ambiguous	0.22	Likely Benign	0.078	Likely Benign	-0.64	Neutral	0.120	Benign	0.182	Benign	3.41	Benign	1.00	Tolerated			0.4853	0.2996		1	1	2.6	-16.00
c.1921T>G	S641A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S641A is not reported in ClinVar and is absent from gnomAD. Across the available in‑silico predictors, every tool examined (REVEL, FoldX, Rosetta, premPS, PROVEAN, polyPhen‑2 HumDiv/HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) uniformly classifies the substitution as benign. No pathogenic predictions are present. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields “Likely Benign”; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also reports a benign effect. Consequently, the variant is most likely benign based on current predictions, and this assessment does not contradict any ClinVar status (none available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.125101	Structured	0.157322	Uncertain	0.786	0.270	0.000											-6.103	Likely Benign	0.092	Likely Benign	Likely Benign	0.37	Likely Benign	0.2	-0.28	Likely Benign	0.05	Likely Benign	0.27	Likely Benign	0.067	Likely Benign	-2.07	Neutral	0.000	Benign	0.001	Benign	3.43	Benign	0.17	Tolerated			0.4873	0.4680		1	1	2.6	-16.00
c.1975T>G	S659A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S659A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign, while ESM1b remains uncertain. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized is benign; the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is benign; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also reports a benign effect. Consequently, the variant is most likely benign, and this assessment does not contradict any ClinVar annotation (none available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.067594	Structured	0.154597	Uncertain	0.954	0.283	0.000											-7.066	In-Between	0.117	Likely Benign	Likely Benign	-0.31	Likely Benign	0.0	0.02	Likely Benign	-0.15	Likely Benign	0.14	Likely Benign	0.088	Likely Benign	-2.22	Neutral	0.097	Benign	0.114	Benign	3.50	Benign	0.64	Tolerated			0.4842	0.3813		1	1	2.6	-16.00
c.1994A>T	Y665F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y665F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only ESM1b predicts a pathogenic outcome, while Rosetta and Foldetta are uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” status. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely benign, and Foldetta as uncertain. Overall, the preponderance of evidence points to a benign impact. This conclusion is consistent with the absence of a ClinVar claim; there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.098513	Structured	0.086641	Uncertain	0.922	0.361	0.000											-8.460	Likely Pathogenic	0.100	Likely Benign	Likely Benign	0.07	Likely Benign	0.1	1.03	Ambiguous	0.55	Ambiguous	0.38	Likely Benign	0.106	Likely Benign	-1.23	Neutral	0.159	Benign	0.036	Benign	3.45	Benign	0.47	Tolerated			0.2277	0.3076		7	3	4.1	-16.00
c.19T>G	S7A 2D AIThe SynGAP1 missense variant S7A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The high‑accuracy consensus, SGM‑Consensus, is derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, all of which are benign, so the consensus is benign. AlphaMissense‑Optimized also predicts benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the available predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.590140	Disordered	0.548467	Binding	0.386	0.922	0.750											-3.613	Likely Benign	0.072	Likely Benign	Likely Benign										0.137	Likely Benign	-0.10	Neutral	0.002	Benign	0.001	Benign	4.18	Benign	0.00	Affected			0.5485	0.4355	Weaken	1	1	2.6	-16.00
c.2002T>G	S668A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 S668A missense variant is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, Rosetta, premPS, SIFT, FATHMM, AlphaMissense‑Optimized, and Foldetta. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. Two tools—AlphaMissense‑Default and FoldX—return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic. Taking all evidence together, the majority of predictions (seven benign versus four pathogenic) and the two high‑accuracy benign calls suggest that the variant is most likely benign. This conclusion does not contradict ClinVar status, as the variant has no ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.247041	Structured	0.084935	Uncertain	0.922	0.370	0.000											-12.011	Likely Pathogenic	0.506	Ambiguous	Likely Benign	0.73	Ambiguous	0.3	-0.44	Likely Benign	0.15	Likely Benign	0.48	Likely Benign	0.399	Likely Benign	-2.99	Deleterious	0.887	Possibly Damaging	0.738	Possibly Damaging	3.28	Benign	0.19	Tolerated			0.4866	0.3967		1	1	2.6	-16.00
c.2045A>T	Y682F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y682F is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b. The SGM Consensus, which is a majority vote among AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two benign vs. two pathogenic votes) and is treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta (combining FoldX‑MD and Rosetta outputs) as benign, and the SGM Consensus remains unavailable. Overall, the balance of evidence—both from general predictors and from the high‑accuracy tools—leans toward a benign classification. This conclusion does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.206376	Structured	0.141467	Uncertain	0.758	0.328	0.000											-9.740	Likely Pathogenic	0.225	Likely Benign	Likely Benign	0.21	Likely Benign	0.1	-0.09	Likely Benign	0.06	Likely Benign	0.42	Likely Benign	0.278	Likely Benign	-3.72	Deleterious	0.997	Probably Damaging	0.947	Probably Damaging	3.40	Benign	0.04	Affected			0.2452	0.3662		7	3	4.1	-16.00
c.2068T>G	S690A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S690A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, Rosetta, premPS, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta reports an uncertain stability change, so these results are treated as unavailable. Overall, the balance of evidence favors a benign interpretation, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.055536	Structured	0.247926	Uncertain	0.944	0.253	0.000											-8.763	Likely Pathogenic	0.318	Likely Benign	Likely Benign	-0.82	Ambiguous	0.0	-2.17	Stabilizing	-1.50	Ambiguous	0.45	Likely Benign	0.217	Likely Benign	-2.55	Deleterious	0.887	Possibly Damaging	0.738	Possibly Damaging	3.45	Benign	0.21	Tolerated			0.4619	0.3131		1	1	2.6	-16.00
c.2254T>G	S752A 2D AIThe SynGAP1 missense variant S752A has no ClinVar record and is not listed in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none exists). Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.604312	Disordered	0.690594	Binding	0.365	0.877	0.625											-3.258	Likely Benign	0.092	Likely Benign	Likely Benign										0.074	Likely Benign	-1.42	Neutral	0.910	Possibly Damaging	0.524	Possibly Damaging	1.59	Pathogenic	0.04	Affected			0.5092	0.5634	Strenghten	1	1	2.6	-16.00
c.226T>G	S76A 2D AIThe SynGAP1 missense variant S76A is reported in gnomAD (ID 6‑33425834‑T‑G) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.517562	Disordered	0.444487	Uncertain	0.279	0.826	0.500								6-33425834-T-G	1	6.20e-7	-3.230	Likely Benign	0.072	Likely Benign	Likely Benign										0.048	Likely Benign	-1.10	Neutral	0.643	Possibly Damaging	0.277	Benign	3.86	Benign	0.00	Affected	4.32	1	0.4543	0.3619		1	1	2.6	-16.00
c.2273A>T	Y758F 2D AIThe SynGAP1 missense variant Y758F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only polyPhen‑2 HumDiv predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are not available. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.517562	Disordered	0.856063	Binding	0.289	0.871	0.375											-1.431	Likely Benign	0.090	Likely Benign	Likely Benign										0.112	Likely Benign	-0.79	Neutral	0.679	Possibly Damaging	0.371	Benign	2.75	Benign	1.00	Tolerated			0.2441	0.2835		7	3	4.1	-16.00
c.2296T>G	S766A 2D AIThe SynGAP1 missense variant S766A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect. The variant is most likely benign, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.405110	Structured	0.923125	Binding	0.338	0.874	0.250											-6.115	Likely Benign	0.186	Likely Benign	Likely Benign										0.055	Likely Benign	-0.98	Neutral	0.447	Benign	0.198	Benign	4.17	Benign	0.02	Affected			0.5059	0.5705	Strenghten	1	1	2.6	-16.00
c.2311T>G	S771A 2D AIThe SynGAP1 missense variant S771A is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Benign.” Foldetta results are unavailable. Overall, the consensus of all available predictions points to a benign impact, and this conclusion is consistent with the lack of a ClinVar classification—there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.436924	Structured	0.922503	Binding	0.306	0.883	0.250											-4.337	Likely Benign	0.107	Likely Benign	Likely Benign										0.067	Likely Benign	-1.09	Neutral	0.025	Benign	0.014	Benign	4.09	Benign	0.62	Tolerated			0.5201	0.4745	Weaken	1	1	2.6	-16.00
c.2338T>G	S780A 2D AIThe SynGAP1 missense variant S780A is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only polyPhen‑2 HumDiv predicts a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence indicates that S780A is most likely benign, and this conclusion is consistent with the lack of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.599170	Disordered	0.812415	Binding	0.283	0.883	0.500											-5.627	Likely Benign	0.164	Likely Benign	Likely Benign										0.072	Likely Benign	-0.40	Neutral	0.798	Possibly Damaging	0.340	Benign	2.69	Benign	0.74	Tolerated			0.4936	0.5522		1	1	2.6	-16.00
c.2362T>G	S788A 2D AIThe SynGAP1 missense variant S788A is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus also as benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact for S788A. This consensus does not contradict ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.956248	Disordered	0.573557	Binding	0.349	0.895	0.750											-5.381	Likely Benign	0.255	Likely Benign	Likely Benign										0.088	Likely Benign	-2.24	Neutral	0.979	Probably Damaging	0.982	Probably Damaging	1.59	Pathogenic	0.02	Affected			0.5079	0.5041	Strenghten	1	1	2.6	-16.00
c.2420A>T	Y807F 2D AIThe SynGAP1 missense variant Y807F is listed in ClinVar (ID 1491782.0) with an “Uncertain” status and is not reported in gnomAD. All evaluated in‑silico predictors classify the substitution as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all return benign scores, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely benign effect. No tool in the set predicts pathogenicity. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (derived from the four high‑accuracy predictors) is benign. Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, has no available result for this variant. Overall, the computational evidence strongly supports a benign impact, and this conclusion does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.699094	Disordered	0.853760	Binding	0.336	0.901	0.500					Uncertain		1				-3.667	Likely Benign	0.073	Likely Benign	Likely Benign										0.057	Likely Benign	0.14	Neutral	0.012	Benign	0.022	Benign	2.92	Benign	0.98	Tolerated	3.77	5	0.2485	0.2500		7	3	4.1	-16.00
c.2446T>G	S816A 2D AIThe SynGAP1 missense variant S816A is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The only tools that predict a pathogenic outcome are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is Likely Benign; Foldetta results are not available. Based on the collective predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.476583	Structured	0.747189	Binding	0.347	0.898	0.375											-4.543	Likely Benign	0.310	Likely Benign	Likely Benign										0.078	Likely Benign	-1.07	Neutral	0.953	Possibly Damaging	0.799	Possibly Damaging	2.67	Benign	0.59	Tolerated			0.5307	0.4532	Weaken	1	1	2.6	-16.00
c.2449T>G	S817A 2D AIThe SynGAP1 missense variant S817A is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also resolves to benign, while Foldetta results are unavailable. Overall, the majority of high‑confidence predictions indicate a benign impact. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.490133	Structured	0.727082	Binding	0.314	0.901	0.625											-6.321	Likely Benign	0.429	Ambiguous	Likely Benign										0.116	Likely Benign	-1.86	Neutral	0.977	Probably Damaging	0.846	Possibly Damaging	2.45	Pathogenic	0.00	Affected			0.5207	0.5866	Strenghten	1	1	2.6	-16.00
c.2459A>T	Y820F 2D AIThe SynGAP1 missense variant Y820F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict a pathogenic impact. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect for Y820F, and this conclusion does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.733139	Disordered	0.695550	Binding	0.293	0.883	0.625											-4.686	Likely Benign	0.301	Likely Benign	Likely Benign										0.111	Likely Benign	-1.67	Neutral	0.990	Probably Damaging	0.893	Possibly Damaging	2.69	Benign	0.21	Tolerated			0.2398	0.2636		7	3	4.1	-16.00
c.2473T>G	S825A 2D AIThe SynGAP1 missense variant S825A is not reported in ClinVar (no entry) and is absent from gnomAD. Prediction tools that agree on benign include REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized. Tools that agree on pathogenic are polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive because it yields a 2‑to‑2 split. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta, has no available result for this variant. Overall, the majority of standard predictors indicate a pathogenic effect, while the high‑accuracy AlphaMissense‑Optimized suggests benign and the consensus is neutral. Given the preponderance of pathogenic predictions and the lack of conflicting evidence from ClinVar or population databases, the variant is most likely pathogenic, with no contradiction to ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.675549	Disordered	0.618614	Binding	0.384	0.886	0.750											-4.878	Likely Benign	0.569	Likely Pathogenic	Likely Benign										0.135	Likely Benign	-2.30	Neutral	0.992	Probably Damaging	0.987	Probably Damaging	2.04	Pathogenic	0.05	Affected			0.4794	0.5749		1	1	2.6	-16.00
c.2524T>G	S842A 2D AIThe SynGAP1 missense variant S842A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further show AlphaMissense‑Optimized as Benign, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Overall, the majority of predictions (seven pathogenic vs. three benign) indicate a pathogenic impact. This conclusion is not contradicted by ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.604312	Disordered	0.617281	Binding	0.274	0.861	0.250											-13.601	Likely Pathogenic	0.656	Likely Pathogenic	Likely Benign										0.180	Likely Benign	-2.37	Neutral	0.889	Possibly Damaging	0.614	Possibly Damaging	2.09	Pathogenic	0.00	Affected			0.3971	0.4223		1	1	2.6	-16.00
c.2581T>G	S861A 2D AIThe SynGAP1 missense variant S861A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Based on the collective predictions, the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.557691	Disordered	0.540903	Binding	0.285	0.797	0.250											-5.059	Likely Benign	0.092	Likely Benign	Likely Benign										0.043	Likely Benign	-1.02	Neutral	0.409	Benign	0.172	Benign	4.08	Benign	0.48	Tolerated			0.4541	0.5401		1	1	2.6	-16.00
c.259T>G	S87A 2D AIThe SynGAP1 missense variant S87A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default, while ESM1b remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also favors benign. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the balance of evidence (six benign predictions versus two pathogenic) indicates that the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.690604	Disordered	0.550904	Binding	0.302	0.878	0.500											-7.817	In-Between	0.676	Likely Pathogenic	Likely Benign										0.039	Likely Benign	-1.24	Neutral	0.140	Benign	0.097	Benign	3.84	Benign	0.00	Affected			0.4272	0.3540		1	1	2.6	-16.00
c.2614T>G	S872A 2D AIThe SynGAP1 missense variant S872A is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The only tools that predict a pathogenic outcome are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments further support a benign prediction: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is Likely Benign; Foldetta results are not available. Overall, the majority of evidence points to a benign effect for S872A, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.486429	Structured	0.662664	Binding	0.262	0.865	0.125											-4.574	Likely Benign	0.170	Likely Benign	Likely Benign										0.105	Likely Benign	-0.91	Neutral	0.979	Probably Damaging	0.982	Probably Damaging	2.77	Benign	0.28	Tolerated			0.5351	0.4945	Weaken	1	1	2.6	-16.00
c.2626T>G	S876A 2D AIThe SynGAP1 missense variant S876A is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.549308	Disordered	0.631130	Binding	0.280	0.872	0.250											-4.228	Likely Benign	0.154	Likely Benign	Likely Benign										0.091	Likely Benign	-1.43	Neutral	0.979	Probably Damaging	0.982	Probably Damaging	2.63	Benign	0.54	Tolerated			0.4495	0.5889		1	1	2.6	-16.00
c.2674T>G	S892A 2D AIThe SynGAP1 missense variant S892A is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus also as likely benign; the Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of evidence—including the consensus and high‑accuracy predictions—supports a benign classification, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.754692	Disordered	0.473390	Uncertain	0.319	0.926	0.875											-3.867	Likely Benign	0.188	Likely Benign	Likely Benign										0.037	Likely Benign	-1.45	Neutral	0.889	Possibly Damaging	0.682	Possibly Damaging	2.63	Benign	0.02	Affected			0.5131	0.4481	Weaken	1	1	2.6	-16.00
c.2689T>G	S897A 2D AIThe SynGAP1 missense variant S897A is not reported in ClinVar and is absent from gnomAD. All evaluated in‑silico predictors—including REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the change as benign. No tool predicts pathogenicity. The high‑accuracy consensus methods likewise support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta results are unavailable. Consequently, the variant is most likely benign based on the collective predictions, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.699094	Disordered	0.418474	Uncertain	0.292	0.928	0.500											-3.959	Likely Benign	0.122	Likely Benign	Likely Benign										0.060	Likely Benign	-0.48	Neutral	0.288	Benign	0.208	Benign	2.71	Benign	0.81	Tolerated			0.4539	0.5684		1	1	2.6	-16.00
c.2692T>G	S898A 2D AIThe SynGAP1 missense variant S898A is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in silico tools cluster around a benign effect: REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) all indicate a likely benign outcome. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT predict a pathogenic impact. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized scores the variant as benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also reports a likely benign classification. No Foldetta stability analysis is available for this residue. Overall, the preponderance of evidence from both general and high‑accuracy predictors suggests that S898A is most likely benign, and this conclusion is consistent with the absence of a ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.690604	Disordered	0.426070	Uncertain	0.305	0.922	0.500											-3.932	Likely Benign	0.146	Likely Benign	Likely Benign										0.052	Likely Benign	-0.98	Neutral	0.942	Possibly Damaging	0.748	Possibly Damaging	2.63	Benign	0.03	Affected			0.4552	0.5516		1	1	2.6	-16.00
c.2776T>G	S926A 2D AIThe SynGAP1 missense variant S926A is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM; AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also favors a benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta, has no available result for this variant. Overall, the majority of reliable predictions indicate a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.461924	Structured	0.981753	Binding	0.295	0.854	0.250											-3.042	Likely Benign	0.463	Ambiguous	Likely Benign										0.186	Likely Benign	-2.13	Neutral	0.992	Probably Damaging	0.987	Probably Damaging	1.59	Pathogenic	0.00	Affected			0.4657	0.4488		1	1	2.6	-16.00
c.2863T>G	S955A 2D AIThe SynGAP1 missense variant S955A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and FATHMM. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.984871	Disordered	0.945325	Binding	0.350	0.924	0.750											-4.258	Likely Benign	0.068	Likely Benign	Likely Benign										0.091	Likely Benign	-0.71	Neutral	0.004	Benign	0.006	Benign	2.41	Pathogenic	0.00	Affected			0.4262	0.5038		1	1	2.6	-16.00
c.2866T>G	S956A 2D AIThe SynGAP1 missense variant S956A is not reported in ClinVar or gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify it as benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as likely benign. Only FATHMM predicts a pathogenic outcome. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta stability analysis is unavailable. Overall, the collective evidence indicates that the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.984871	Disordered	0.957345	Binding	0.364	0.917	0.750											-4.468	Likely Benign	0.087	Likely Benign	Likely Benign										0.111	Likely Benign	-0.47	Neutral	0.112	Benign	0.039	Benign	2.18	Pathogenic	0.13	Tolerated			0.4239	0.4838		1	1	2.6	-16.00
c.2945A>T	Y982F 2D AIThe SynGAP1 missense variant Y982F is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while the single pathogenic prediction comes from SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates a benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.707965	Disordered	0.966717	Binding	0.272	0.895	0.625											-3.431	Likely Benign	0.208	Likely Benign	Likely Benign										0.154	Likely Benign	-0.36	Neutral	0.006	Benign	0.009	Benign	4.63	Benign	0.00	Affected			0.2351	0.2980		7	3	4.1	-16.00
c.2965T>G	S989A 2D AIThe SynGAP1 missense variant S989A is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus also indicates Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.795062	Disordered	0.908835	Binding	0.296	0.911	0.750											-3.495	Likely Benign	0.089	Likely Benign	Likely Benign										0.083	Likely Benign	-1.15	Neutral	0.580	Possibly Damaging	0.253	Benign	2.68	Benign	0.00	Affected			0.4580	0.4221		1	1	2.6	-16.00
c.2968T>G	S990A 2D AIThe SynGAP1 missense variant S990A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (majority vote) also indicates Likely Benign. Foldetta results are unavailable. Overall, the majority of computational evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.816150	Disordered	0.902387	Binding	0.301	0.919	0.750											-3.554	Likely Benign	0.063	Likely Benign	Likely Benign										0.020	Likely Benign	-0.51	Neutral	0.001	Benign	0.004	Benign	2.91	Benign	0.03	Affected			0.4537	0.4509		1	1	2.6	-16.00
c.2995T>G	S999A 2D AIThe SynGAP1 missense variant S999A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Benign.” Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of all available predictions is that the variant is most likely benign, and this conclusion is consistent with the lack of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.834292	Disordered	0.950682	Binding	0.262	0.897	0.625											-3.719	Likely Benign	0.075	Likely Benign	Likely Benign										0.051	Likely Benign	-0.83	Neutral	0.005	Benign	0.016	Benign	2.71	Benign	0.81	Tolerated			0.4516	0.5434		1	1	2.6	-16.00
c.299A>T	Y100F 2D AIThe SynGAP1 missense variant Y100F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.699094	Disordered	0.675421	Binding	0.341	0.880	0.625											-3.056	Likely Benign	0.117	Likely Benign	Likely Benign										0.139	Likely Benign	-0.50	Neutral	0.928	Possibly Damaging	0.222	Benign	4.21	Benign	0.00	Affected			0.2784	0.3087		7	3	4.1	-16.00
c.3017A>T	Y1006F 2D AIThe SynGAP1 missense variant Y1006F is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only two tools, polyPhen‑2 HumDiv and HumVar, predict pathogenic. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact, and this is consistent with the lack of ClinVar annotation, so there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.801317	Disordered	0.930554	Binding	0.264	0.896	0.750											-3.362	Likely Benign	0.304	Likely Benign	Likely Benign										0.083	Likely Benign	-1.06	Neutral	0.999	Probably Damaging	0.992	Probably Damaging	2.71	Benign	0.10	Tolerated			0.2423	0.3339		7	3	4.1	-16.00
c.3037T>G	S1013A 2D AIThe SynGAP1 missense variant S1013A is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Benign.” Foldetta results are unavailable. Overall, the consensus of all available predictions points to a benign impact, and this conclusion is consistent with the lack of a ClinVar classification, so there is no contradiction. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.823549	Disordered	0.899570	Binding	0.308	0.846	0.625											-3.400	Likely Benign	0.070	Likely Benign	Likely Benign										0.049	Likely Benign	-0.89	Neutral	0.001	Benign	0.002	Benign	2.71	Benign	0.30	Tolerated			0.4728	0.5131		1	1	2.6	-16.00
c.3067T>G	S1023A 2D AIThe SynGAP1 missense variant S1023A is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in silico tools cluster around a benign effect: REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized all indicate benign, while the majority of pathogenic predictors—polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT—suggest a damaging impact. The AlphaMissense‑Default score is uncertain, and Foldetta stability analysis is unavailable. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign outcome. High‑accuracy tools therefore lean toward a benign interpretation: AlphaMissense‑Optimized predicts benign, SGM‑Consensus indicates likely benign, and no Foldetta data is available. Overall, the computational evidence supports a benign classification, with no conflict with ClinVar status because no ClinVar assertion exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.831250	Disordered	0.990262	Binding	0.322	0.750	0.500											-6.031	Likely Benign	0.356	Ambiguous	Likely Benign										0.098	Likely Benign	-1.59	Neutral	0.979	Probably Damaging	0.982	Probably Damaging	2.53	Benign	0.04	Affected			0.4427	0.4386		1	1	2.6	-16.00
c.3097T>G	S1033A 2D AIThe SynGAP1 missense variant S1033A is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Benign.” Foldetta results are unavailable. Overall, the consensus of all available predictions indicates that the variant is most likely benign, and this conclusion is consistent with the lack of a ClinVar classification, so there is no contradiction. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.910643	Disordered	0.993473	Binding	0.294	0.737	0.625											-3.107	Likely Benign	0.121	Likely Benign	Likely Benign										0.033	Likely Benign	0.06	Neutral	0.220	Benign	0.085	Benign	2.81	Benign	1.00	Tolerated			0.4387	0.5282		1	1	2.6	-16.00
c.3139T>G	S1047A 2D AIThe SynGAP1 missense variant S1047A is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Benign.” Foldetta results are unavailable. Overall, the consensus of all available predictions indicates that the variant is most likely benign, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.963420	Disordered	0.933764	Binding	0.409	0.909	0.750											-3.503	Likely Benign	0.060	Likely Benign	Likely Benign										0.040	Likely Benign	-0.50	Neutral	0.001	Benign	0.002	Benign	2.65	Benign	0.07	Tolerated			0.4460	0.5548		1	1	2.6	-16.00
c.313T>G	S105A 2D AIThe SynGAP1 missense variant S105A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect. The predictions do not contradict ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.788093	Disordered	0.669201	Binding	0.364	0.870	0.625											-3.779	Likely Benign	0.115	Likely Benign	Likely Benign										0.046	Likely Benign	-0.67	Neutral	0.012	Benign	0.002	Benign	4.11	Benign	0.00	Affected			0.5299	0.4214	Weaken	1	1	2.6	-16.00
c.3217T>G	S1073A 2D AIThe SynGAP1 missense variant S1073A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as benign, while only SIFT predicts it as pathogenic. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) confirms a benign status. Foldetta’s protein‑folding stability analysis is unavailable for this variant. Overall, the preponderance of evidence from multiple prediction algorithms and high‑accuracy tools suggests that the variant is most likely benign, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.916840	Disordered	0.985818	Binding	0.313	0.905	0.750											-5.333	Likely Benign	0.220	Likely Benign	Likely Benign										0.104	Likely Benign	-0.96	Neutral	0.447	Benign	0.103	Benign	3.95	Benign	0.02	Affected			0.4571	0.5883		1	1	2.6	-16.00
c.3259T>G	S1087A 2D AIThe SynGAP1 missense variant S1087A is not reported in ClinVar and is absent from gnomAD, indicating no documented clinical or population data. Functional prediction tools uniformly classify the variant as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a benign effect. No tool in the dataset indicates pathogenicity. High‑accuracy assessments corroborate this benign prediction: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta results are unavailable. Based on the consensus of all available predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.912647	Disordered	0.974805	Binding	0.357	0.891	1.000											-3.649	Likely Benign	0.076	Likely Benign	Likely Benign										0.057	Likely Benign	-1.03	Neutral	0.447	Benign	0.139	Benign	2.64	Benign	0.34	Tolerated			0.4464	0.5405		1	1	2.6	-16.00
c.3280T>G	S1094A 2D AIThe SynGAP1 missense variant S1094A is not reported in ClinVar and is absent from gnomAD, indicating no documented allele frequency data. Functional prediction tools uniformly classify the variant as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a benign effect. No tool in the dataset indicates pathogenicity, so the pathogenic‑prediction group is empty. High‑accuracy assessments corroborate this benign prediction: AlphaMissense‑Optimized reports benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a “Likely Benign” verdict. Foldetta results are not available, so they do not influence the assessment. Overall, the variant is most likely benign, and this conclusion is consistent with the lack of ClinVar evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.938133	Disordered	0.981352	Binding	0.358	0.877	1.000											-3.595	Likely Benign	0.188	Likely Benign	Likely Benign										0.117	Likely Benign	-0.78	Neutral	0.447	Benign	0.252	Benign	2.66	Benign	1.00	Tolerated			0.4692	0.5403		1	1	2.6	-16.00
c.3296A>T	Y1099F 2D AIThe SynGAP1 missense variant Y1099F is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Overall, the consensus of all available predictions points to a benign impact, and this is consistent with the lack of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.885302	Disordered	0.974267	Binding	0.400	0.862	1.000											-3.651	Likely Benign	0.101	Likely Benign	Likely Benign										0.082	Likely Benign	-0.85	Neutral	0.006	Benign	0.008	Benign	2.75	Benign	0.27	Tolerated			0.2453	0.2780		7	3	4.1	-16.00
c.3394T>G	S1132A 2D AIThe SynGAP1 missense variant S1132A is not reported in ClinVar and is absent from gnomAD, indicating no documented population frequency. Functional prediction tools uniformly classify the variant as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a benign effect. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized reports a benign outcome, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign status. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of all available predictions is that the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.919029	Disordered	0.845506	Binding	0.289	0.894	0.750											-3.401	Likely Benign	0.078	Likely Benign	Likely Benign										0.213	Likely Benign	-0.60	Neutral	0.061	Benign	0.013	Benign	5.47	Benign	0.55	Tolerated			0.4416	0.5683		1	1	2.6	-16.00
c.3412T>G	S1138A 2D AIThe SynGAP1 missense variant S1138A is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only the two polyPhen‑2 implementations (HumDiv and HumVar) predict a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.891961	Disordered	0.738250	Binding	0.346	0.869	1.000											-5.821	Likely Benign	0.105	Likely Benign	Likely Benign										0.354	Likely Benign	-0.99	Neutral	0.979	Probably Damaging	0.982	Probably Damaging	5.47	Benign	0.24	Tolerated			0.4387	0.5748		1	1	2.6	-16.00
c.3424T>G	S1142A 2D AIThe SynGAP1 missense variant S1142A is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while only SIFT predicts it to be pathogenic. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports the variant as “Likely Benign.” High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) confirms a benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence indicates that S1142A is most likely benign, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.919029	Disordered	0.719935	Binding	0.276	0.844	1.000											-3.694	Likely Benign	0.085	Likely Benign	Likely Benign										0.074	Likely Benign	-1.31	Neutral	0.002	Benign	0.015	Benign	2.73	Benign	0.00	Affected			0.4689	0.5319		1	1	2.6	-16.00
c.3451T>G	S1151A 2D AIThe SynGAP1 missense variant S1151A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only the two polyPhen‑2 implementations (HumDiv and HumVar) predict a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” consensus. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Based on the preponderance of evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.741537	Disordered	0.805072	Binding	0.394	0.839	0.625											-3.311	Likely Benign	0.077	Likely Benign	Likely Benign										0.084	Likely Benign	-0.13	Neutral	0.889	Possibly Damaging	0.535	Possibly Damaging	2.75	Benign	0.42	Tolerated			0.4711	0.5087		1	1	2.6	-16.00
c.3475T>G	S1159A 2D AIThe SynGAP1 missense variant S1159A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also reports it as likely benign. In contrast, polyPhen‑2 (HumDiv and HumVar) predict the variant to be pathogenic. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.626927	Disordered	0.867068	Binding	0.343	0.846	0.375											-3.653	Likely Benign	0.327	Likely Benign	Likely Benign										0.095	Likely Benign	-0.46	Neutral	0.979	Probably Damaging	0.982	Probably Damaging	2.71	Benign	0.44	Tolerated			0.4754	0.4541		1	1	2.6	-16.00
c.347A>T	Y116F 2D AIThe SynGAP1 missense variant Y116F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only polyPhen‑2 HumDiv predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates a benign likelihood. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.661982	Disordered	0.670235	Binding	0.381	0.878	0.625											-2.911	Likely Benign	0.119	Likely Benign	Likely Benign										0.048	Likely Benign	-0.71	Neutral	0.539	Possibly Damaging	0.042	Benign	4.21	Benign	0.33	Tolerated			0.2632	0.3069		7	3	4.1	-16.00
c.3493T>G	S1165A 2D AIThe SynGAP1 missense variant S1165A is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in silico tools cluster around a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all indicate benign, while the majority of other predictors (polyPhen‑2 HumDiv and HumVar) suggest pathogenic. When predictions are grouped by agreement, the benign‑predicating tools outnumber the pathogenic ones, and the single uncertain call from AlphaMissense‑Default does not alter this balance. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized classifies the variant as benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports it as Likely Benign. Foldetta data are unavailable. Overall, the computational evidence points to a benign effect, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.509769	Disordered	0.835017	Binding	0.308	0.807	0.375											-3.308	Likely Benign	0.476	Ambiguous	Likely Benign										0.106	Likely Benign	-1.11	Neutral	0.979	Probably Damaging	0.982	Probably Damaging	2.61	Benign	0.60	Tolerated			0.5363	0.4236	Weaken	1	1	2.6	-16.00
c.3533A>T	Y1178F 2D AIThe SynGAP1 missense variant Y1178F is not reported in ClinVar and is absent from gnomAD, indicating no documented clinical or population data. Functional prediction tools uniformly classify the variant as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a benign effect. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely benign outcome. Foldetta results are unavailable. Based on the consensus of all available predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.541878	Disordered	0.568433	Binding	0.554	0.688	0.250											-3.081	Likely Benign	0.131	Likely Benign	Likely Benign										0.162	Likely Benign	-0.64	Neutral	0.012	Benign	0.017	Benign	5.44	Benign	0.24	Tolerated			0.1893	0.2758		7	3	4.1	-16.00
c.3548A>T	Y1183F 2D AIThe SynGAP1 missense variant Y1183F is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all classify the change as benign, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports it as likely benign. In contrast, polyPhen‑2 (HumDiv and HumVar) predict a pathogenic impact. The AlphaMissense‑Default score is uncertain, and no Foldetta stability assessment is available. High‑accuracy methods give a benign consensus: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign, with no Foldetta data. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.566480	Disordered	0.527818	Binding	0.523	0.652	0.500											-3.527	Likely Benign	0.446	Ambiguous	Likely Benign										0.124	Likely Benign	-1.42	Neutral	0.951	Possibly Damaging	0.514	Possibly Damaging	2.74	Benign	0.23	Tolerated			0.1891	0.2829		7	3	4.1	-16.00
c.3550T>G	S1184A 2D AIThe SynGAP1 missense variant S1184A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools are divided: benign predictions come from REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” outcome. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) also indicates benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.648219	Disordered	0.514669	Binding	0.624	0.642	0.500											-3.753	Likely Benign	0.595	Likely Pathogenic	Likely Benign										0.107	Likely Benign	-1.11	Neutral	0.979	Probably Damaging	0.973	Probably Damaging	2.73	Benign	0.51	Tolerated			0.4093	0.3850		1	1	2.6	-16.00
c.3556T>G	S1186A 2D AIThe SynGAP1 missense variant S1186A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic outcome are AlphaMissense‑Default, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; a Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.562014	Disordered	0.506433	Binding	0.634	0.636	0.625											-5.226	Likely Benign	0.572	Likely Pathogenic	Likely Benign										0.115	Likely Benign	-1.45	Neutral	0.979	Probably Damaging	0.982	Probably Damaging	2.69	Benign	0.16	Tolerated			0.4636	0.3487		1	1	2.6	-16.00
c.3593A>T	Y1198F 2D AIThe SynGAP1 missense variant Y1198F is not reported in ClinVar and has no entry in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and SIFT, while pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, and AlphaMissense‑Default. Two tools—ESM1b and AlphaMissense‑Optimized—return uncertain results. High‑accuracy assessments further support a deleterious effect: the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) labels the variant as Likely Pathogenic, and AlphaMissense‑Optimized remains uncertain; Foldetta, a protein‑folding stability method, has no available output for this variant. Overall, the preponderance of evidence (five pathogenic vs. two benign predictions) indicates that the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently contains no classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.626927	Disordered	0.439379	Uncertain	0.853	0.593	0.250											-7.508	In-Between	0.853	Likely Pathogenic	Ambiguous										0.219	Likely Benign	-2.87	Deleterious	0.999	Probably Damaging	0.992	Probably Damaging	1.55	Pathogenic	0.13	Tolerated			0.1780	0.2571		7	3	4.1	-16.00
c.3610T>G	S1204A 2D AIThe SynGAP1 missense variant S1204A is not reported in ClinVar and is absent from gnomAD, indicating no known population frequency data. Functional prediction tools uniformly classify the substitution as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a neutral effect. No tool in the dataset indicates pathogenicity. High‑accuracy assessments corroborate this benign prediction: AlphaMissense‑Optimized reports a benign outcome, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a “Likely Benign” classification. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the collective evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.595080	Disordered	0.541098	Binding	0.887	0.587	0.375											-5.134	Likely Benign	0.144	Likely Benign	Likely Benign										0.213	Likely Benign	-0.53	Neutral	0.061	Benign	0.047	Benign	5.45	Benign	1.00	Tolerated			0.4943	0.3167		1	1	2.6	-16.00
c.3634T>G	S1212A 2D AIThe SynGAP1 missense variant S1212A is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized, whereas polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM all predict a pathogenic outcome; AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields benign, and Foldetta results are unavailable. Consequently, the collective evidence points to a benign classification for S1212A, and this conclusion does not conflict with the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.566480	Disordered	0.548409	Binding	0.852	0.565	0.500											-4.705	Likely Benign	0.403	Ambiguous	Likely Benign										0.109	Likely Benign	-1.66	Neutral	0.992	Probably Damaging	0.987	Probably Damaging	2.27	Pathogenic	0.00	Affected			0.3901	0.3823		1	1	2.6	-16.00
c.3656A>T	Y1219F 2D AIThe SynGAP1 missense variant Y1219F is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default—consistently predict a pathogenic impact. High‑accuracy assessments show that the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic outcome, while AlphaMissense‑Optimized remains uncertain. No Foldetta stability data are available, so it does not influence the assessment. Overall, the preponderance of evidence points to a pathogenic effect for Y1219F, and this conclusion does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.613573	Disordered	0.474748	Uncertain	0.855	0.557	0.375											-7.202	In-Between	0.837	Likely Pathogenic	Ambiguous										0.272	Likely Benign	-2.79	Deleterious	0.999	Probably Damaging	0.992	Probably Damaging	2.23	Pathogenic	0.00	Affected			0.1998	0.2583		7	3	4.1	-16.00
c.3673T>G	S1225A 2D AIThe SynGAP1 missense variant S1225A is not reported in ClinVar and is absent from gnomAD, indicating no known clinical annotation or population frequency data. Functional prediction tools uniformly classify the variant as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a benign effect. No tool in the dataset indicates pathogenicity. The high‑accuracy consensus, SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the evidence strongly supports a benign classification, and this assessment does not contradict any ClinVar status, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.513880	Disordered	0.441915	Uncertain	0.891	0.544	0.500											-3.157	Likely Benign	0.089	Likely Benign	Likely Benign										0.257	Likely Benign	-0.16	Neutral	0.139	Benign	0.089	Benign	5.51	Benign	1.00	Tolerated			0.3804	0.3823		1	1	2.6	-16.00
c.3710A>T	Y1237F 2D AIThe SynGAP1 missense variant Y1237F is not reported in ClinVar and has no entries in gnomAD, indicating it is not catalogued in these databases. Prediction tools that classify the variant as benign include REVEL and ESM1b, whereas the majority of other in silico predictors—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default—label it pathogenic. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely pathogenic outcome. High‑accuracy assessments are mixed: AlphaMissense‑Optimized returns an uncertain result, SGM‑Consensus confirms a likely pathogenic prediction, and Foldetta data are unavailable. Based on the preponderance of pathogenic predictions and the SGM‑Consensus outcome, the variant is most likely pathogenic. This assessment does not contradict ClinVar status, as no ClinVar entry exists for Y1237F. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.653063	Disordered	0.563444	Binding	0.842	0.535	0.125											-4.494	Likely Benign	0.864	Likely Pathogenic	Ambiguous										0.268	Likely Benign	-3.12	Deleterious	0.999	Probably Damaging	0.992	Probably Damaging	1.55	Pathogenic	0.00	Affected			0.1938	0.2424		7	3	4.1	-16.00
c.3769T>G	S1257A 2D AIThe SynGAP1 missense variant S1257A is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only polyPhen‑2 HumDiv predicts it as pathogenic, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Benign.” High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign, and the SGM‑Consensus also reports a benign likelihood. Foldetta results are unavailable, so they do not influence the conclusion. Overall, the preponderance of evidence points to a benign impact for S1257A, and this assessment is consistent with the lack of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.541878	Disordered	0.482380	Uncertain	0.889	0.572	0.375											-3.937	Likely Benign	0.096	Likely Benign	Likely Benign										0.118	Likely Benign	-1.02	Neutral	0.454	Possibly Damaging	0.266	Benign	2.64	Benign	0.26	Tolerated			0.4083	0.3800		1	1	2.6	-16.00
c.385T>G	S129A 2D AIThe SynGAP1 missense variant S129A is not reported in ClinVar and is absent from gnomAD. All evaluated in‑silico predictors—including REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the change as benign. No tool predicts pathogenicity. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign effect. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus itself is benign; Foldetta results are unavailable. Consequently, the variant is most likely benign based on the collective predictions, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.517562	Disordered	0.713635	Binding	0.311	0.880	0.625											-3.388	Likely Benign	0.134	Likely Benign	Likely Benign										0.090	Likely Benign	-0.08	Neutral	0.007	Benign	0.007	Benign	4.21	Benign	0.15	Tolerated			0.5031	0.4619	Weaken	1	1	2.6	-16.00
c.418T>G	S140A 2D AIThe SynGAP1 missense variant S140A is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM, while those that agree on a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized tool rates the variant as uncertain, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive due to a 2‑to‑2 split; Foldetta results are unavailable. Overall, the majority of predictions (five pathogenic vs. three benign) indicate a pathogenic impact. There is no ClinVar entry to contradict this assessment, so the variant is most likely pathogenic based on the available computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.476583	Structured	0.587898	Binding	0.321	0.896	0.625											-9.068	Likely Pathogenic	0.805	Likely Pathogenic	Ambiguous										0.141	Likely Benign	-1.83	Neutral	0.956	Probably Damaging	0.931	Probably Damaging	3.62	Benign	0.05	Affected			0.4449	0.4320		1	1	2.6	-16.00
c.436T>G	S146A 2D AIThe SynGAP1 missense variant S146A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 pathogenic vs. 2 benign). Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. This conclusion does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.541878	Disordered	0.508612	Binding	0.349	0.837	0.625											-14.042	Likely Pathogenic	0.721	Likely Pathogenic	Likely Benign										0.097	Likely Benign	-1.81	Neutral	0.000	Benign	0.002	Benign	3.71	Benign	0.00	Affected			0.4435	0.3708		1	1	2.6	-16.00
c.49T>G	S17A 2D AIThe SynGAP1 missense variant S17A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (majority vote) also indicates Likely Benign. Foldetta results are unavailable. Overall, the majority of computational evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.483068	Structured	0.452228	Uncertain	0.341	0.910	0.375											-3.140	Likely Benign	0.166	Likely Benign	Likely Benign										0.078	Likely Benign	-0.34	Neutral	0.000	Benign	0.000	Benign	4.15	Benign	0.00	Affected			0.5276	0.5824	Strenghten	1	1	2.6	-16.00
c.538T>G	S180A 2D AIThe SynGAP1 missense variant S180A is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and ESM1b, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a benign majority (2 benign vs. 1 pathogenic). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence indicates that the S180A variant is most likely benign, and this conclusion does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.509769	Disordered	0.442877	Uncertain	0.320	0.616	0.500											-10.413	Likely Pathogenic	0.559	Ambiguous	Likely Benign										0.095	Likely Benign	-1.94	Neutral	0.390	Benign	0.079	Benign	3.90	Benign	0.04	Affected			0.5003	0.3788	Weaken	1	1	2.6	-16.00
c.53A>T	Y18F 2D AIThe SynGAP1 missense variant Y18F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.483068	Structured	0.446314	Uncertain	0.345	0.908	0.375											-2.371	Likely Benign	0.160	Likely Benign	Likely Benign										0.059	Likely Benign	-0.19	Neutral	0.115	Benign	0.018	Benign	4.18	Benign	0.00	Affected			0.2675	0.3322		7	3	4.1	-16.00
c.544T>G	S182A 2D AIThe SynGAP1 missense variant S182A is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that predict a pathogenic effect are SIFT, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a 2‑vs‑2 tie, and Foldetta results are unavailable. Overall, the majority of standard predictors lean toward a benign impact, and no ClinVar evidence contradicts this assessment. Thus, the variant is most likely benign based on current predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.501700	Disordered	0.436016	Uncertain	0.368	0.619	0.625											-9.417	Likely Pathogenic	0.838	Likely Pathogenic	Ambiguous										0.113	Likely Benign	-2.26	Neutral	0.001	Benign	0.005	Benign	3.70	Benign	0.00	Affected			0.5466	0.4660	Weaken	1	1	2.6	-16.00
c.553T>G	S185A 2D AIThe SynGAP1 missense variant S185A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that predict a pathogenic effect are PROVEAN, SIFT, ESM1b, and AlphaMissense‑Default, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic outcome. AlphaMissense‑Optimized is uncertain, and no Foldetta stability result is available. High‑accuracy assessments therefore show a likely pathogenic consensus from SGM‑Consensus, with no contradictory evidence from ClinVar or population databases. Based on the collective predictions, the variant is most likely pathogenic, and this assessment does not contradict any existing ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.545602	Disordered	0.430485	Uncertain	0.365	0.623	0.500											-11.839	Likely Pathogenic	0.868	Likely Pathogenic	Ambiguous										0.203	Likely Benign	-2.57	Deleterious	0.231	Benign	0.107	Benign	3.65	Benign	0.00	Affected			0.5147	0.4472	Weaken	1	1	2.6	-16.00
c.610T>G	S204A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S204A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome; the only inconclusive results come from Rosetta, Foldetta, and premPS, which are treated as unavailable evidence. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Benign, and Foldetta as Uncertain. Overall, the variant is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	PH	0.268042	Structured	0.420667	Uncertain	0.816	0.405	0.125											-3.330	Likely Benign	0.084	Likely Benign	Likely Benign	-0.09	Likely Benign	0.0	-1.17	Ambiguous	-0.63	Ambiguous	-0.83	Ambiguous	0.091	Likely Benign	0.65	Neutral	0.004	Benign	0.004	Benign	4.28	Benign	0.27	Tolerated			0.3706	0.3495		1	1	2.6	-16.00
c.634T>G	S212A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S212A has no ClinVar record and is not listed in gnomAD. Prediction tools cluster into two groups: benign predictions come from FoldX, Rosetta, Foldetta, PROVEAN, and FATHMM, while pathogenic predictions arise from REVEL, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Two tools report uncertainty: premPS and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive due to a 2‑vs‑2 split, and Foldetta predicts benign stability. Overall, the majority of conventional tools lean toward pathogenicity, whereas the most reliable high‑accuracy methods are either benign or inconclusive. Thus, the variant is most likely pathogenic based on the prevailing predictions, and this assessment does not contradict ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		PH	0.158265	Structured	0.381517	Uncertain	0.846	0.278	0.125											-8.890	Likely Pathogenic	0.869	Likely Pathogenic	Ambiguous	-0.13	Likely Benign	0.1	0.13	Likely Benign	0.00	Likely Benign	0.75	Ambiguous	0.752	Likely Pathogenic	-2.48	Neutral	0.956	Probably Damaging	0.931	Probably Damaging	5.83	Benign	0.01	Affected			0.4639	0.4509		1	1	2.6	-16.00
c.673T>G	S225A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S225A is not reported in ClinVar and has no entry in gnomAD. Functional prediction tools uniformly indicate a benign effect: REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool predicts pathogenicity. The high‑accuracy assessments corroborate this: AlphaMissense‑Optimized is benign; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is also benign. Foldetta, which integrates FoldX‑MD and Rosetta outputs, is inconclusive (uncertain) and therefore does not alter the overall benign assessment. Consequently, the variant is most likely benign based on the available predictions, and this conclusion is not contradicted by ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	PH	0.150080	Structured	0.344191	Uncertain	0.817	0.319	0.250											-3.752	Likely Benign	0.052	Likely Benign	Likely Benign	0.31	Likely Benign	0.3	0.79	Ambiguous	0.55	Ambiguous	0.11	Likely Benign	0.201	Likely Benign	-1.52	Neutral	0.001	Benign	0.001	Benign	5.79	Benign	0.58	Tolerated			0.4840	0.5897		1	1	2.6	-16.00
c.676T>G	S226A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S226A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Functional prediction tools uniformly indicate a benign effect: REVEL, FoldX, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all classify the variant as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, the SGM‑Consensus predicts likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts benign. Consequently, the variant is most likely benign based on current predictions, and this assessment does not contradict any ClinVar status (none available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	PH	0.129801	Structured	0.334959	Uncertain	0.800	0.324	0.250											-4.665	Likely Benign	0.117	Likely Benign	Likely Benign	0.06	Likely Benign	0.0	0.25	Likely Benign	0.16	Likely Benign	-0.02	Likely Benign	0.339	Likely Benign	-1.64	Neutral	0.123	Benign	0.050	Benign	5.76	Benign	0.06	Tolerated			0.4812	0.5599		1	1	2.6	-16.00
c.703T>G	S235A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S235A has no ClinVar entry and is not present in gnomAD. Prediction tools that indicate benign effects include Rosetta, premPS, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Optimized. Those that predict pathogenicity are REVEL, PROVEAN, SIFT, ESM1b, and AlphaMissense‑Default. FoldX and Foldetta return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—classifies the variant as pathogenic; Foldetta remains uncertain. Overall, the balance of evidence leans toward a benign interpretation, but the SGM Consensus introduces a pathogenic signal, resulting in a conflicting prediction profile. This assessment does not contradict ClinVar status, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.250310	Structured	0.319150	Uncertain	0.743	0.331	0.000											-10.861	Likely Pathogenic	0.707	Likely Pathogenic	Likely Benign	1.92	Ambiguous	0.1	0.19	Likely Benign	1.06	Ambiguous	0.48	Likely Benign	0.646	Likely Pathogenic	-2.52	Deleterious	0.002	Benign	0.004	Benign	5.49	Benign	0.01	Affected			0.5168	0.4563	Weaken	1	1	2.6	-16.00
c.82T>G	S28A 2D AIThe SynGAP1 missense variant S28A is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely benign outcome. No pathogenic predictions are present among the evaluated tools. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise indicates likely benign; Foldetta results are unavailable. Consequently, the variant is most likely benign based on the collective predictions, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.545602	Disordered	0.438157	Uncertain	0.354	0.884	0.125											-3.517	Likely Benign	0.063	Likely Benign	Likely Benign										0.039	Likely Benign	0.09	Neutral	0.000	Benign	0.000	Benign	4.27	Benign	1.00	Tolerated			0.5194	0.4958	Weaken	1	1	2.6	-16.00
c.839A>T	Y280F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y280F is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. The remaining tools—premPS, ESM1b, and AlphaMissense‑Default—return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, while the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive and therefore unavailable. Overall, the majority of available predictions favor a pathogenic impact, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.161087	Structured	0.321243	Uncertain	0.917	0.248	0.125											-7.844	In-Between	0.414	Ambiguous	Likely Benign	0.49	Likely Benign	0.2	0.03	Likely Benign	0.26	Likely Benign	0.87	Ambiguous	0.544	Likely Pathogenic	-3.68	Deleterious	0.999	Probably Damaging	0.992	Probably Damaging	1.98	Pathogenic	0.02	Affected			0.2263	0.2398		7	3	4.1	-16.00
c.842A>T	Y281F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y281F is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, Rosetta, premPS, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign, while polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM predict pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely benign outcome. High‑accuracy assessments further support this: AlphaMissense‑Optimized predicts benign; Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts benign. No evidence from the uncertain FoldX result is considered. Overall, the consensus of high‑confidence tools points to a benign classification, which is consistent with the absence of ClinVar evidence and gnomAD data. Thus, the variant is most likely benign, and this conclusion does not contradict ClinVar status, which has no reported pathogenicity. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.098513	Structured	0.337647	Uncertain	0.927	0.254	0.000											-3.991	Likely Benign	0.146	Likely Benign	Likely Benign	0.75	Ambiguous	0.2	-0.26	Likely Benign	0.25	Likely Benign	-0.37	Likely Benign	0.372	Likely Benign	-0.32	Neutral	0.999	Probably Damaging	0.992	Probably Damaging	1.17	Pathogenic	0.54	Tolerated			0.2380	0.3885		7	3	4.1	-16.00
c.872A>T	Y291F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y291F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, FoldX, Rosetta, Foldetta, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign) all predict a neutral impact. In contrast, polyPhen‑2 (HumDiv and HumVar) and FATHMM predict a pathogenic effect, while premPS remains uncertain. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized is benign; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Benign; and Foldetta (combining FoldX‑MD and Rosetta outputs) is benign. Overall, the majority of evidence supports a benign classification, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.173081	Structured	0.383842	Uncertain	0.912	0.251	0.000											-4.095	Likely Benign	0.305	Likely Benign	Likely Benign	-0.43	Likely Benign	0.1	-0.10	Likely Benign	-0.27	Likely Benign	0.71	Ambiguous	0.148	Likely Benign	-2.31	Neutral	0.999	Probably Damaging	0.992	Probably Damaging	1.77	Pathogenic	0.27	Tolerated			0.2362	0.3441		7	3	4.1	-16.00
c.886T>G	S296A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S296A (ClinVar ID 469166.0) is listed as ClinVar status Uncertain and is not present in gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign or neutral. In contrast, polyPhen‑2 (HumDiv and HumVar) and FATHMM predict pathogenic. Grouping by consensus, the benign‑predicting tools outnumber the pathogenic ones. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is also benign; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, reports a benign effect. No evidence from the available tools suggests a deleterious impact. Therefore, the variant is most likely benign, and this conclusion is consistent with its ClinVar status of Uncertain rather than pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.444081	Structured	0.282669	Uncertain	0.887	0.284	0.250					Uncertain		1				-6.847	Likely Benign	0.247	Likely Benign	Likely Benign	0.50	Ambiguous	0.3	-0.26	Likely Benign	0.12	Likely Benign	0.35	Likely Benign	0.209	Likely Benign	-1.79	Neutral	0.992	Probably Damaging	0.987	Probably Damaging	1.97	Pathogenic	0.65	Tolerated	3.40	16	0.4958	0.5522		1	1	2.6	-16.00	182.5	26.6	-0.2	0.1	-0.5	0.0		X						Potentially Pathogenic	The hydroxyl group of the Ser296 side chain, located in an anti-parallel β sheet strand (res. Met289-Pro298), stably hydrogen bonds with the carboxylate group of Asp330 in a neighboring β strand (res. Ala322-Asp332). The backbone carbonyl group of Ser296 also hydrogen bonds with the guanidinium group of Arg279 in another nearby β strand (res. Arg279-Cys285). In the variant simulations, the methyl group of the Ala296 side chain cannot hydrogen bond with Asp330, causing the carboxylate group positioning to fluctuate more than in the WT simulations.Although the residue swap does not seem to affect the anti-parallel β sheet assembly during the simulations, it is possible that the Ser296-Asp330 hydrogen bond plays a crucial role in maintaining the C2 domain fold. Notably, because Ser296 is located near the membrane interface, the potential effect of the residue swap on the SynGAP-membrane association cannot be addressed by solvent-only simulations.
c.898T>G	S300A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S300A is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only FATHMM predicts a pathogenic outcome. Rosetta and Foldetta give uncertain results and are therefore not considered evidence for either side. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is also benign (3 benign vs. 1 pathogenic). Foldetta remains uncertain. Overall, the preponderance of evidence indicates that the variant is most likely benign, and this conclusion does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.356642	Structured	0.256848	Uncertain	0.742	0.280	0.375											-5.420	Likely Benign	0.060	Likely Benign	Likely Benign	0.08	Likely Benign	0.3	1.07	Ambiguous	0.58	Ambiguous	0.08	Likely Benign	0.031	Likely Benign	-1.18	Neutral	0.139	Benign	0.060	Benign	1.56	Pathogenic	0.20	Tolerated			0.5135	0.4949	Weaken	1	1	2.6	-16.00
c.904T>G	S302A 2D AIThe SynGAP1 missense variant S302A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and Foldetta. No tool predicts a pathogenic outcome; the only inconclusive result is from Rosetta, which is treated as unavailable. High‑accuracy assessments reinforce the benign prediction: AlphaMissense‑Optimized is benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) is benign. Based on the collective evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar status because the variant is not currently catalogued in ClinVar. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.414856	Structured	0.263489	Uncertain	0.616	0.258	0.375											-2.583	Likely Benign	0.058	Likely Benign	Likely Benign	0.21	Likely Benign	0.4	0.65	Ambiguous	0.43	Likely Benign	0.02	Likely Benign	0.044	Likely Benign	-0.41	Neutral	0.000	Benign	0.001	Benign	4.16	Benign	0.20	Tolerated			0.5358	0.5407	Strenghten	1	1	2.6	-16.00
c.983A>T	Y328F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y328F is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, SIFT, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM; AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.411940	Structured	0.392519	Uncertain	0.916	0.497	0.000											-6.770	Likely Benign	0.444	Ambiguous	Likely Benign	0.34	Likely Benign	0.1	0.43	Likely Benign	0.39	Likely Benign	0.37	Likely Benign	0.330	Likely Benign	-3.21	Deleterious	0.999	Probably Damaging	0.992	Probably Damaging	1.67	Pathogenic	0.16	Tolerated			0.2409	0.3643		7	3	4.1	-16.00
c.991T>G	S331A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S331A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only FATHMM predicts pathogenic. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a benign majority vote (3 benign vs. 1 pathogenic). High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign; the SGM‑Consensus (majority vote) is benign; and Foldetta, combining FoldX‑MD and Rosetta outputs, is benign. No prediction or folding‑stability result is missing or inconclusive. Based on the collective evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.433034	Structured	0.346458	Uncertain	0.658	0.475	0.250											-2.199	Likely Benign	0.101	Likely Benign	Likely Benign	0.22	Likely Benign	0.1	-0.08	Likely Benign	0.07	Likely Benign	-0.15	Likely Benign	0.071	Likely Benign	-0.44	Neutral	0.139	Benign	0.060	Benign	1.89	Pathogenic	0.67	Tolerated			0.5314	0.3008	Weaken	1	1	2.6	-16.00
c.1013A>T	D338V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D338V missense variant is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only premPS, whereas the remaining tools—SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—consistently predict pathogenicity. High‑accuracy methods give the following results: AlphaMissense‑Optimized is uncertain; the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) is uncertain. No prediction or folding‑stability result is missing or inconclusive. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.335645	Structured	0.363354	Uncertain	0.460	0.438	0.375											-11.494	Likely Pathogenic	0.927	Likely Pathogenic	Ambiguous	1.64	Ambiguous	0.2	1.08	Ambiguous	1.36	Ambiguous	0.23	Likely Benign	0.553	Likely Pathogenic	-6.79	Deleterious	0.891	Possibly Damaging	0.492	Possibly Damaging	1.73	Pathogenic	0.01	Affected			0.0879	0.5745		-2	-3	7.7	-15.96
c.119A>T	D40V 2D AIThe SynGAP1 missense variant D40V is not reported in ClinVar and is absent from gnomAD, indicating no known population frequency data. Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized scores the variant as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely benign effect. No Foldetta stability prediction is available for this variant. Overall, the majority of computational evidence points to a benign impact, and this conclusion does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.384043	Structured	0.432002	Uncertain	0.319	0.769	0.375											-3.350	Likely Benign	0.431	Ambiguous	Likely Benign										0.222	Likely Benign	-1.16	Neutral	0.028	Benign	0.088	Benign	4.00	Benign	0.00	Affected			0.1679	0.8357		-2	-3	7.7	-15.96
c.1388A>T	D463V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant D463V is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include FoldX, premPS, SIFT, and FATHMM, whereas those that agree on a pathogenic effect are SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and AlphaMissense‑Default. Uncertain predictions come from Rosetta, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the majority of evidence points toward a pathogenic impact for D463V, and this conclusion does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.260850	Structured	0.305622	Uncertain	0.940	0.176	0.000											-12.374	Likely Pathogenic	0.880	Likely Pathogenic	Ambiguous	0.23	Likely Benign	0.1	0.98	Ambiguous	0.61	Ambiguous	0.33	Likely Benign	0.521	Likely Pathogenic	-7.95	Deleterious	0.973	Probably Damaging	0.658	Possibly Damaging	3.31	Benign	0.09	Tolerated			0.0713	0.5526		-2	-3	7.7	-15.96
c.1400A>T	D467V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D467V missense variant is not reported in ClinVar or gnomAD. Prediction tools cluster into two groups: benign predictions come from Rosetta and premPS, while the majority—SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—label the change as pathogenic. Two tools, FoldX and Foldetta, give uncertain results. High‑accuracy assessments reinforce the pathogenic signal: AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus indicates likely pathogenic, and Foldetta remains uncertain. Overall, the consensus of high‑confidence predictors points to a pathogenic effect, and this conclusion is consistent with the absence of any ClinVar annotation or gnomAD observation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.268042	Structured	0.329932	Uncertain	0.940	0.246	0.000											-15.041	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	1.24	Ambiguous	0.1	0.08	Likely Benign	0.66	Ambiguous	0.02	Likely Benign	0.893	Likely Pathogenic	-8.70	Deleterious	0.997	Probably Damaging	0.997	Probably Damaging	-1.28	Pathogenic	0.02	Affected			0.0644	0.5274		-2	-3	7.7	-15.96
c.1421A>T	D474V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D474V missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that indicate a benign effect include Rosetta, Foldetta, and premPS, whereas the majority of tools predict a pathogenic impact: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). FoldX is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic, and Foldetta as benign. Overall, the balance of evidence favors a pathogenic classification, and this conclusion does not contradict any ClinVar annotation because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.102787	Structured	0.373433	Uncertain	0.864	0.255	0.000											-12.999	Likely Pathogenic	0.988	Likely Pathogenic	Likely Pathogenic	0.77	Ambiguous	0.0	0.18	Likely Benign	0.48	Likely Benign	0.18	Likely Benign	0.866	Likely Pathogenic	-7.69	Deleterious	0.998	Probably Damaging	0.997	Probably Damaging	-1.30	Pathogenic	0.04	Affected			0.0694	0.4510		-2	-3	7.7	-15.96
c.1523A>T	D508V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D508V missense change is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL, FoldX, premPS, SIFT, FATHMM, AlphaMissense‑Optimized, and Foldetta. Those that predict pathogenicity are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (a folding‑stability method combining FoldX‑MD and Rosetta outputs) as benign. With seven benign versus six pathogenic calls and two of the three high‑accuracy tools supporting benign, the variant is most likely benign. This conclusion does not contradict the ClinVar status, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.019401	Structured	0.255890	Uncertain	0.890	0.228	0.000											-13.529	Likely Pathogenic	0.691	Likely Pathogenic	Likely Benign	0.07	Likely Benign	0.1	0.66	Ambiguous	0.37	Likely Benign	0.07	Likely Benign	0.381	Likely Benign	-8.37	Deleterious	0.985	Probably Damaging	0.895	Possibly Damaging	3.27	Benign	0.08	Tolerated			0.1050	0.4604		-2	-3	7.7	-15.96
c.1580A>T	D527V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D527V missense variant is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a pathogenic effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that are uncertain (FoldX, Rosetta, Foldetta, premPS) provide no definitive evidence. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, while Foldetta remains uncertain. Overall, the majority of reliable predictors classify the variant as pathogenic, and this conclusion does not contradict any ClinVar annotation because no ClinVar entry exists. Thus, based on current computational evidence, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.139895	Structured	0.021908	Uncertain	0.913	0.408	0.000											-16.844	Likely Pathogenic	0.985	Likely Pathogenic	Likely Pathogenic	0.71	Ambiguous	0.7	0.84	Ambiguous	0.78	Ambiguous	-0.55	Ambiguous	0.938	Likely Pathogenic	-8.78	Deleterious	0.998	Probably Damaging	0.997	Probably Damaging	-2.40	Pathogenic	0.00	Affected			0.0659	0.3984		-2	-3	7.7	-15.96
c.1748A>T	D583V 2D 3DClick to see structure in 3D Viewer AISynGAP1 D583V is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include Rosetta, Foldetta, premPS, and SIFT, whereas pathogenic predictions are made by SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; FoldX and ESM1b give uncertain results. High‑accuracy methods give a split view: AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) predicts benign. Overall, the majority of tools support a pathogenic effect, and this is consistent with the lack of ClinVar annotation; there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.116183	Structured	0.038478	Uncertain	0.805	0.247	0.000											-7.796	In-Between	0.973	Likely Pathogenic	Likely Pathogenic	1.20	Ambiguous	0.2	-0.31	Likely Benign	0.45	Likely Benign	0.12	Likely Benign	0.839	Likely Pathogenic	-8.63	Deleterious	0.999	Probably Damaging	0.999	Probably Damaging	-1.40	Pathogenic	0.08	Tolerated			0.0778	0.4090		-2	-3	7.7	-15.96
c.1757A>T	D586V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant D586V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that classify the variant as benign include FoldX, Rosetta, Foldetta, premPS, and SIFT. Tools that predict pathogenicity include SGM‑Consensus (Likely Pathogenic), REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of predictions (nine pathogenic vs. five benign) indicate a pathogenic effect. This conclusion is not contradicted by ClinVar status, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.060549	Structured	0.066018	Uncertain	0.866	0.241	0.000											-12.409	Likely Pathogenic	0.977	Likely Pathogenic	Likely Pathogenic	0.40	Likely Benign	0.2	0.03	Likely Benign	0.22	Likely Benign	0.18	Likely Benign	0.801	Likely Pathogenic	-5.58	Deleterious	0.998	Probably Damaging	0.999	Probably Damaging	-1.23	Pathogenic	0.24	Tolerated			0.0826	0.5458		-2	-3	7.7	-15.96
c.179A>T	D60V 2D AIThe SynGAP1 D60V missense variant is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM. Tools that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 vs 2), and Foldetta results are unavailable. Overall, the majority of evaluated predictors (7 of 10) indicate pathogenicity, while only three suggest benignity. Therefore, the variant is most likely pathogenic based on current computational evidence, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.284882	Structured	0.480942	Uncertain	0.521	0.676	0.000											-6.576	Likely Benign	0.980	Likely Pathogenic	Likely Pathogenic										0.254	Likely Benign	-2.72	Deleterious	0.972	Probably Damaging	0.954	Probably Damaging	3.91	Benign	0.00	Affected			0.0765	0.7962		-2	-3	7.7	-15.96
c.1847A>T	D616V 2D 3DClick to see structure in 3D Viewer AISynGAP1 D616V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL, premPS, and FATHMM, while pathogenic calls are made by FoldX, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus. Uncertain results are reported by Rosetta and AlphaMissense‑Optimized. High‑accuracy assessments give a pathogenic signal: AlphaMissense‑Optimized is inconclusive, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. Overall, the majority of evidence, including the high‑accuracy tools, supports a pathogenic effect for D616V. This conclusion is not contradicted by ClinVar, which has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.129801	Structured	0.166689	Uncertain	0.867	0.252	0.000											-13.992	Likely Pathogenic	0.919	Likely Pathogenic	Ambiguous	2.41	Destabilizing	0.2	1.95	Ambiguous	2.18	Destabilizing	0.36	Likely Benign	0.268	Likely Benign	-7.36	Deleterious	0.972	Probably Damaging	0.682	Possibly Damaging	3.26	Benign	0.00	Affected			0.0699	0.4393		-2	-3	7.7	-15.96
c.185A>T	D62V 2D AIThe SynGAP1 missense variant D62V is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in‑silico tools cluster around a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized all indicate a benign outcome, while the sole pathogenic signal comes from SIFT. AlphaMissense‑Default remains uncertain, and no Foldetta stability assessment is available. High‑accuracy methods reinforce the benign consensus: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports Likely Benign, and Foldetta data are missing. Taken together, the preponderance of evidence supports a benign classification for D62V, and this assessment does not conflict with the absence of a ClinVar entry. Therefore, the variant is most likely benign, and this conclusion does not contradict the ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.425610	Structured	0.476010	Uncertain	0.575	0.720	0.125											-4.417	Likely Benign	0.489	Ambiguous	Likely Benign										0.118	Likely Benign	-2.04	Neutral	0.028	Benign	0.088	Benign	4.04	Benign	0.00	Affected			0.1039	0.6129		-2	-3	7.7	-15.96
c.1931A>T	D644V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D644V missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Rosetta, premPS, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive because it yields a 2‑to‑2 split. Overall, the majority of evidence points to a benign impact. Thus, the variant is most likely benign, and this conclusion does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.066181	Structured	0.248888	Uncertain	0.883	0.320	0.000											-6.230	Likely Benign	0.636	Likely Pathogenic	Likely Benign	0.50	Ambiguous	0.0	-0.35	Likely Benign	0.08	Likely Benign	-0.03	Likely Benign	0.347	Likely Benign	-4.96	Deleterious	0.198	Benign	0.052	Benign	3.49	Benign	0.11	Tolerated			0.0951	0.6267		-2	-3	7.7	-15.96
c.2012A>T	D671V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D671V missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include REVEL, premPS, and FATHMM. Tools that predict a pathogenic effect include PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy consensus methods give a pathogenic signal: AlphaMissense‑Optimized is pathogenic, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is also pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is uncertain. Overall, the majority of predictions (seven pathogenic vs. three benign) support a pathogenic classification. There is no ClinVar entry to contradict this assessment, so the variant is most likely pathogenic based on the available computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.194234	Structured	0.096749	Uncertain	0.677	0.370	0.000											-12.376	Likely Pathogenic	0.963	Likely Pathogenic	Likely Pathogenic	0.63	Ambiguous	0.1	0.51	Ambiguous	0.57	Ambiguous	0.14	Likely Benign	0.379	Likely Benign	-6.08	Deleterious	0.975	Probably Damaging	0.885	Possibly Damaging	3.31	Benign	0.01	Affected			0.0820	0.6651		-2	-3	7.7	-15.96
c.2051A>T	D684V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant D684V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: pathogenic calls come from REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized, while only premPS and FATHMM predict a benign outcome. High‑accuracy assessments reinforce the pathogenic interpretation: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) is pathogenic. No evidence suggests a benign effect, and the lack of ClinVar annotation means there is no conflicting clinical classification. Therefore, the variant is most likely pathogenic, with no contradiction to ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.254060	Structured	0.153798	Uncertain	0.870	0.282	0.000											-16.128	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	3.86	Destabilizing	1.1	2.06	Destabilizing	2.96	Destabilizing	0.07	Likely Benign	0.601	Likely Pathogenic	-8.98	Deleterious	0.901	Possibly Damaging	0.480	Possibly Damaging	3.44	Benign	0.00	Affected			0.0775	0.6209		-2	-3	7.7	-15.96
c.212A>T	D71V 2D AIThe SynGAP1 D71V missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, resolves to a likely benign classification (3 benign vs. 1 pathogenic votes). High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.575842	Disordered	0.456046	Uncertain	0.350	0.799	0.375											-3.549	Likely Benign	0.780	Likely Pathogenic	Likely Benign										0.183	Likely Benign	-2.28	Neutral	0.334	Benign	0.060	Benign	4.01	Benign	0.00	Affected			0.0771	0.6197		-2	-3	7.7	-15.96
c.2159A>T	D720V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant D720V has no ClinVar entry and is not reported in gnomAD. Prediction tools that classify it as benign include REVEL, FoldX, Foldetta, and premPS, whereas pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM Consensus score (Likely Pathogenic). High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, Foldetta as benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Pathogenic. Overall, the majority of evidence points to a pathogenic effect, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.374039	Structured	0.450695	Uncertain	0.955	0.417	0.125											-12.730	Likely Pathogenic	0.941	Likely Pathogenic	Ambiguous	0.08	Likely Benign	0.0	-0.78	Ambiguous	-0.35	Likely Benign	0.20	Likely Benign	0.437	Likely Benign	-7.18	Deleterious	0.999	Probably Damaging	0.999	Probably Damaging	2.12	Pathogenic	0.00	Affected			0.0822	0.5708		-2	-3	7.7	-15.96
c.2285A>T	D762V 2D AIThe SynGAP1 D762V missense variant is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and ESM1b. Tools that agree on a pathogenic effect include polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized tool returned an uncertain result, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 pathogenic vs. 2 benign). Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the majority of consensus tools predict a pathogenic impact, and there is no ClinVar entry to contradict this assessment. Thus, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.405110	Structured	0.910475	Binding	0.308	0.859	0.125											-6.122	Likely Benign	0.949	Likely Pathogenic	Ambiguous										0.229	Likely Benign	-1.98	Neutral	0.999	Probably Damaging	0.977	Probably Damaging	2.08	Pathogenic	0.01	Affected			0.1105	0.8785		-2	-3	7.7	-15.96
c.2303A>T	D768V 2D AIThe SynGAP1 D768V variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is unavailable for this variant. Based on the preponderance of pathogenic predictions and the SGM‑Consensus result, the variant is most likely pathogenic; this assessment does not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.332115	Structured	0.928237	Binding	0.314	0.877	0.250											-9.528	Likely Pathogenic	0.880	Likely Pathogenic	Ambiguous										0.164	Likely Benign	-2.62	Deleterious	0.611	Possibly Damaging	0.140	Benign	4.04	Benign	0.02	Affected			0.0802	0.8019		-2	-3	7.7	-15.96
c.2345A>T	D782V 2D AIThe SynGAP1 missense variant D782V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (which reports “Likely Pathogenic”). The high‑accuracy AlphaMissense‑Optimized tool yields an uncertain result, and the Foldetta stability assessment is unavailable. Overall, the consensus of the available predictions strongly favors a pathogenic effect for D782V. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.604312	Disordered	0.768342	Binding	0.285	0.883	0.625											-8.250	Likely Pathogenic	0.931	Likely Pathogenic	Ambiguous										0.462	Likely Benign	-3.59	Deleterious	0.999	Probably Damaging	0.979	Probably Damaging	1.92	Pathogenic	0.00	Affected			0.0803	0.6477		-2	-3	7.7	-15.96
c.2411A>T	D804V 2D AIThe SynGAP1 missense variant D804V is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus—predict a pathogenic impact. The AlphaMissense‑Optimized score is uncertain, providing no definitive evidence. High‑accuracy assessments show that the SGM‑Consensus, which is a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely pathogenic outcome; AlphaMissense‑Optimized remains inconclusive, and Foldetta results are unavailable. Overall, the preponderance of evidence points to a pathogenic effect for D804V, and this conclusion does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.801317	Disordered	0.786762	Binding	0.294	0.900	0.625											-8.143	Likely Pathogenic	0.832	Likely Pathogenic	Ambiguous										0.402	Likely Benign	-4.77	Deleterious	0.997	Probably Damaging	0.951	Probably Damaging	1.19	Pathogenic	0.01	Affected			0.1196	0.6981		-2	-3	7.7	-15.96
c.2477A>T	D826V 2D AIThe SynGAP1 missense variant D826V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and ESM1b, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments reinforce the pathogenic signal: AlphaMissense‑Optimized predicts pathogenic, and the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—also indicates likely pathogenic. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a pathogenic effect for D826V, and this conclusion does not conflict with ClinVar, which currently contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.666105	Disordered	0.627309	Binding	0.327	0.886	0.625											-6.918	Likely Benign	0.991	Likely Pathogenic	Likely Pathogenic										0.428	Likely Benign	-4.64	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.48	Pathogenic	0.00	Affected			0.1017	0.8023		-2	-3	7.7	-15.96
c.2534A>T	D845V 2D AIThe SynGAP1 D845V missense variant is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a deleterious effect: REVEL classifies it as benign, whereas the remaining 11 predictors (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) all predict pathogenicity. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments further support a harmful outcome: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus also indicates Likely Pathogenic; Foldetta results are not available. Taken together, the overwhelming majority of evidence points to a pathogenic effect. This conclusion is consistent with the absence of a ClinVar entry, so there is no contradiction with existing clinical annotations. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.553315	Disordered	0.599971	Binding	0.297	0.827	0.500											-8.914	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic										0.426	Likely Benign	-6.15	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.91	Pathogenic	0.00	Affected			0.0871	0.7088		-2	-3	7.7	-15.96
c.2546A>T	D849V 2D AIThe SynGAP1 missense variant D849V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of computational evidence points to a benign effect, and this is consistent with the lack of any ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.712013	Disordered	0.554191	Binding	0.319	0.813	0.500											-3.819	Likely Benign	0.319	Likely Benign	Likely Benign										0.137	Likely Benign	-2.10	Neutral	0.918	Possibly Damaging	0.481	Possibly Damaging	4.15	Benign	0.00	Affected			0.1161	0.7963		-2	-3	7.7	-15.96
c.2603A>T	D868V 2D AIThe SynGAP1 missense variant D868V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, SIFT, and ESM1b, whereas those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the overall distribution of predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.525368	Disordered	0.676362	Binding	0.262	0.815	0.250											-5.200	Likely Benign	0.853	Likely Pathogenic	Ambiguous										0.182	Likely Benign	-3.17	Deleterious	0.999	Probably Damaging	0.966	Probably Damaging	2.49	Pathogenic	0.25	Tolerated			0.1485	0.6753		-2	-3	7.7	-15.96
c.2741A>T	D914V 2D AIThe SynGAP1 missense variant D914V is listed in ClinVar (ID 2582846.0) with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is “Likely Benign.” High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote) as benign; Foldetta results are unavailable. Overall, the balance of evidence points to a benign effect, and this conclusion does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.699094	Disordered	0.785987	Binding	0.320	0.892	0.250					Uncertain		1				-4.260	Likely Benign	0.723	Likely Pathogenic	Likely Benign										0.187	Likely Benign	-2.24	Neutral	0.999	Probably Damaging	0.986	Probably Damaging	2.64	Benign	0.01	Affected	3.77	5	0.1316	0.7249		-3	-2	7.7	-15.96
c.2810A>T	D937V 2D AIThe SynGAP1 missense variant D937V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also as benign; Foldetta results are unavailable. Overall, the majority of predictions (six benign vs. four pathogenic) support a benign classification. This consensus does not contradict ClinVar status, as no ClinVar entry exists for this variant. Thus, based on current computational evidence, the D937V variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.819762	Disordered	0.963385	Binding	0.348	0.883	0.625											-3.418	Likely Benign	0.673	Likely Pathogenic	Likely Benign										0.141	Likely Benign	-2.21	Neutral	1.000	Probably Damaging	0.977	Probably Damaging	2.70	Benign	0.02	Affected			0.1766	0.7408		-2	-3	7.7	-15.96
c.2921A>T	D974V 2D AIThe SynGAP1 missense variant D974V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus also indicates Likely Benign. Foldetta results are unavailable, so they do not influence the assessment. Overall, the collective predictions strongly suggest that D974V is most likely benign, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.879233	Disordered	0.964377	Binding	0.389	0.897	0.625											-3.629	Likely Benign	0.351	Ambiguous	Likely Benign										0.211	Likely Benign	-1.49	Neutral	0.001	Benign	0.002	Benign	4.16	Benign	0.01	Affected			0.1449	0.7286		-2	-3	7.7	-15.96
c.2960A>T	D987V 2D AIThe SynGAP1 missense variant D987V is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and ESM1b, while pathogenic predictions are made by PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is uncertain, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels the variant as Likely Pathogenic. No Foldetta stability data are available, so it does not influence the assessment. Overall, the preponderance of evidence indicates that D987V is most likely pathogenic, and this conclusion is not contradicted by ClinVar status, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.823549	Disordered	0.919118	Binding	0.299	0.903	0.750											-4.647	Likely Benign	0.857	Likely Pathogenic	Ambiguous										0.389	Likely Benign	-4.01	Deleterious	0.992	Probably Damaging	0.913	Probably Damaging	2.34	Pathogenic	0.00	Affected			0.0907	0.7202		-2	-3	7.7	-15.96
c.3023A>T	D1008V 2D AIThe SynGAP1 D1008V variant is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM. Those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized tool returns an uncertain result, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (two pathogenic vs. two benign votes). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, more tools (five) predict pathogenicity than benign (three), and the high‑accuracy assessments do not overturn this trend. Therefore, the variant is most likely pathogenic based on current predictions, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.694846	Disordered	0.919416	Binding	0.280	0.899	0.625											-4.828	Likely Benign	0.944	Likely Pathogenic	Ambiguous										0.242	Likely Benign	-3.61	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.64	Benign	0.01	Affected			0.1447	0.6608		-2	-3	7.7	-15.96
c.3047A>T	D1016V 2D AIThe SynGAP1 D1016V missense variant is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools show a split: benign calls come from REVEL and ESM1b, while pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments give an uncertain result from AlphaMissense‑Optimized, a Likely Pathogenic verdict from the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN), and no available data from Foldetta. Overall, the majority of evidence points toward a deleterious effect. Thus, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently has no entry for this change. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.801317	Disordered	0.944705	Binding	0.323	0.811	0.625											-3.208	Likely Benign	0.800	Likely Pathogenic	Ambiguous										0.362	Likely Benign	-3.80	Deleterious	0.977	Probably Damaging	0.856	Possibly Damaging	2.45	Pathogenic	0.00	Affected			0.1424	0.7116		-2	-3	7.7	-15.96
c.3077A>T	D1026V 2D AIThe SynGAP1 missense variant D1026V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. Tools that predict a pathogenic effect are PROVEAN, SIFT, FATHMM, and AlphaMissense‑Default. The high‑accuracy consensus, SGM‑Consensus, is derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN and therefore also indicates a likely pathogenic outcome. AlphaMissense‑Optimized is uncertain, and no Foldetta stability result is available, so it does not contribute evidence. Overall, the majority of reliable predictors classify the variant as pathogenic, and this assessment does not contradict any ClinVar annotation because none exists. Thus, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.894241	Disordered	0.993931	Binding	0.324	0.739	0.500											-5.871	Likely Benign	0.900	Likely Pathogenic	Ambiguous										0.144	Likely Benign	-3.13	Deleterious	0.004	Benign	0.004	Benign	2.48	Pathogenic	0.00	Affected			0.0957	0.5236		-2	-3	7.7	-15.96
c.3500A>T	D1167V 2D AIThe SynGAP1 missense variant D1167V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus is labeled Likely Pathogenic. The Foldetta protein‑folding stability analysis is unavailable for this variant. Based on the preponderance of pathogenic predictions and the high‑accuracy tool results, the variant is most likely pathogenic; this conclusion is not contradicted by any ClinVar status, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.599170	Disordered	0.783999	Binding	0.336	0.798	0.500											-2.750	Likely Benign	0.994	Likely Pathogenic	Likely Pathogenic										0.288	Likely Benign	-3.34	Deleterious	0.999	Probably Damaging	0.977	Probably Damaging	2.26	Pathogenic	0.00	Affected			0.0946	0.7515		-2	-3	7.7	-15.96
c.3563A>T	D1188V 2D AIThe SynGAP1 D1188V missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM, whereas the majority of tools predict a pathogenic outcome: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 vs 2), and Foldetta results are unavailable. Overall, the balance of evidence (seven pathogenic versus three benign predictions) indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.476583	Structured	0.484322	Uncertain	0.687	0.626	0.625											-4.482	Likely Benign	0.993	Likely Pathogenic	Likely Pathogenic										0.479	Likely Benign	-4.13	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	5.49	Benign	0.00	Affected			0.0592	0.4651		-2	-3	7.7	-15.96
c.3578A>T	D1193V 2D AIThe SynGAP1 D1193V missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a pathogenic effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default, while only FATHMM predicts a benign outcome. ESM1b and AlphaMissense‑Optimized are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, whereas the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—leans pathogenic (two pathogenic vs. one benign). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence indicates the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.585406	Disordered	0.433390	Uncertain	0.807	0.600	0.375											-7.297	In-Between	0.855	Likely Pathogenic	Ambiguous										0.526	Likely Pathogenic	-2.92	Deleterious	0.977	Probably Damaging	0.856	Possibly Damaging	5.51	Benign	0.00	Affected			0.0752	0.4174		-2	-3	7.7	-15.96
c.3767A>T	D1256V 2D AIThe SynGAP1 missense variant D1256V is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess functional impact largely agree on a deleterious effect: SIFT, polyPhen‑2 (HumDiv and HumVar), PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as pathogenic, while the only benign prediction comes from REVEL. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports the variant as “Likely Pathogenic.” High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus confirms a likely pathogenic status. Foldetta results are not available, so they do not influence the overall assessment. Based on the preponderance of pathogenic predictions, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.549308	Disordered	0.445789	Uncertain	0.876	0.571	0.625											-14.067	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic										0.446	Likely Benign	-6.89	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.63	Pathogenic	0.00	Affected			0.0573	0.4407		-2	-3	7.7	-15.96
c.3827A>T	D1276V 2D AIThe SynGAP1 D1276V missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default) predict a pathogenic impact. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is unavailable for this variant. Based on the preponderance of pathogenic predictions and the SGM‑Consensus result, the variant is most likely pathogenic. This conclusion is not contradicted by ClinVar status, as no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.666105	Disordered	0.802156	Binding	0.636	0.705	0.625											-0.725	Likely Benign	0.851	Likely Pathogenic	Ambiguous										0.331	Likely Benign	-6.66	Deleterious	0.984	Probably Damaging	0.825	Possibly Damaging	1.19	Pathogenic	0.00	Affected			0.0614	0.5207		-2	-3	7.7	-15.96
c.3878A>T	D1293V 2D AIThe SynGAP1 missense variant D1293V is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 benign vs. 2 pathogenic). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the majority of available predictions (five pathogenic vs. four benign) lean toward a pathogenic impact. This assessment does not contradict ClinVar status, as the variant has not yet been classified in that database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.779859	Disordered	0.892346	Binding	0.569	0.801	0.625											-3.817	Likely Benign	0.328	Likely Benign	Likely Benign										0.343	Likely Benign	-6.03	Deleterious	0.960	Probably Damaging	0.679	Possibly Damaging	2.16	Pathogenic	0.00	Affected			0.0896	0.3603		-2	-3	7.7	-15.96
c.4025A>T	D1342V 2D AIThe SynGAP1 missense variant D1342V is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign and the SGM‑Consensus also indicating a likely benign outcome; the Foldetta protein‑folding stability analysis is unavailable. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.921076	Disordered	0.981682	Binding	0.316	0.678	0.875											-2.890	Likely Benign	0.317	Likely Benign	Likely Benign										0.089	Likely Benign	-1.27	Neutral	0.588	Possibly Damaging	0.212	Benign	4.01	Benign	0.00	Affected			0.1214	0.5617		-2	-3	7.7	-15.96
c.452A>T	D151V 2D AIThe SynGAP1 D151V variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is “Likely Pathogenic” based on a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus is likely pathogenic. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the preponderance of evidence from multiple in silico predictors indicates that D151V is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.529623	Disordered	0.503277	Binding	0.342	0.841	0.625											-11.927	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic										0.380	Likely Benign	-5.19	Deleterious	0.998	Probably Damaging	0.994	Probably Damaging	3.88	Benign	0.00	Affected			0.0864	0.7781		-2	-3	7.7	-15.96
c.500A>T	D167V 2D AIThe SynGAP1 D167V variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that predict a pathogenic impact are PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus also indicates Likely Pathogenic. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of computational evidence points to a pathogenic effect, and this conclusion does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.429200	Structured	0.502306	Binding	0.377	0.667	0.375											-14.388	Likely Pathogenic	0.967	Likely Pathogenic	Likely Pathogenic										0.396	Likely Benign	-4.03	Deleterious	0.535	Possibly Damaging	0.247	Benign	3.92	Benign	0.00	Affected			0.0709	0.6905		-2	-3	7.7	-15.96
c.506A>T	D169V 2D AIThe SynGAP1 D169V missense variant is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL, polyPhen‑2 (HumDiv and HumVar) and FATHMM, while pathogenic calls arise from PROVEAN, SIFT, ESM1b and AlphaMissense‑Default. When predictions are grouped by consensus, four tools predict benign and four predict pathogenic. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized returns an uncertain result, whereas the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM and PROVEAN—labels the variant as Likely Pathogenic. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this residue. Overall, the balance of evidence, particularly the SGM Consensus and the pathogenic calls from multiple independent predictors, indicates that D169V is most likely pathogenic, and this assessment does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.418646	Structured	0.497160	Uncertain	0.420	0.675	0.125											-12.395	Likely Pathogenic	0.925	Likely Pathogenic	Ambiguous										0.243	Likely Benign	-3.77	Deleterious	0.380	Benign	0.193	Benign	4.03	Benign	0.00	Affected			0.0895	0.7166		-2	-3	7.7	-15.96
c.602A>T	D201V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D201V missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, premPS, and FATHMM, while those that predict a pathogenic impact are SGM‑Consensus (Likely Pathogenic), Rosetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Uncertain. With the majority of tools indicating pathogenicity and no ClinVar record to contradict this, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.366687	Structured	0.428570	Uncertain	0.698	0.447	0.125											-10.283	Likely Pathogenic	0.906	Likely Pathogenic	Ambiguous	0.87	Ambiguous	0.1	2.18	Destabilizing	1.53	Ambiguous	0.31	Likely Benign	0.305	Likely Benign	-5.01	Deleterious	0.999	Probably Damaging	0.946	Probably Damaging	4.04	Benign	0.02	Affected			0.0572	0.5207		-2	-3	7.7	-15.96
c.608A>T	D203V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D203V missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, FATHMM, and AlphaMissense‑Optimized, while those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b; AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of tools and the SGM Consensus lean toward a pathogenic interpretation, whereas two high‑accuracy methods (AlphaMissense‑Optimized and Foldetta) suggest benign. Because ClinVar contains no entry for this variant, there is no contradiction between the predictions and existing clinical annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		PH	0.314870	Structured	0.427620	Uncertain	0.740	0.407	0.125											-10.660	Likely Pathogenic	0.523	Ambiguous	Likely Benign	0.32	Likely Benign	0.0	0.44	Likely Benign	0.38	Likely Benign	0.05	Likely Benign	0.289	Likely Benign	-4.07	Deleterious	0.991	Probably Damaging	0.781	Possibly Damaging	3.98	Benign	0.02	Affected			0.0534	0.4084		-2	-3	7.7	-15.96
c.68A>T	D23V 2D AIThe SynGAP1 D23V missense variant is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM. Those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a 2‑vs‑2 tie and thus unavailable; Foldetta predictions are not provided. Overall, more tools (five) predict pathogenicity than benign (three), and no ClinVar evidence contradicts this assessment. Therefore, the variant is most likely pathogenic based on the available predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.557691	Disordered	0.440341	Uncertain	0.369	0.892	0.375											-3.244	Likely Benign	0.842	Likely Pathogenic	Ambiguous										0.137	Likely Benign	-2.72	Deleterious	0.972	Probably Damaging	0.804	Possibly Damaging	3.48	Benign	0.00	Affected			0.1515	0.8367		-2	-3	7.7	-15.96
c.719A>T	D240V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D240V missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include Rosetta, FATHMM, and premPS, whereas the majority of algorithms—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score—classify the change as pathogenic or likely pathogenic. FoldX and Foldetta return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta as uncertain. Overall, the preponderance of evidence points to a pathogenic effect for D240V. This conclusion is not contradicted by ClinVar, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.127496	Structured	0.343480	Uncertain	0.822	0.333	0.000											-15.095	Likely Pathogenic	0.986	Likely Pathogenic	Likely Pathogenic	1.32	Ambiguous	0.1	0.28	Likely Benign	0.80	Ambiguous	0.11	Likely Benign	0.894	Likely Pathogenic	-7.94	Deleterious	0.998	Probably Damaging	0.994	Probably Damaging	5.82	Benign	0.00	Affected			0.0610	0.4949		-2	-3	7.7	-15.96
c.764A>T	D255V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant D255V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: benign predictions come from premPS and FATHMM, while pathogenic predictions are made by SGM‑Consensus (Likely Pathogenic), REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain results are reported by FoldX, Rosetta, and Foldetta. High‑accuracy methods reinforce the pathogenic interpretation: AlphaMissense‑Optimized predicts Pathogenic, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Pathogenic, and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, remains Uncertain. Overall, the consensus of available predictions points to a pathogenic effect for D255V, and this conclusion is consistent with the lack of ClinVar annotation (no contradiction). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.501700	Disordered	0.219132	Uncertain	0.801	0.273	0.250											-13.575	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	1.76	Ambiguous	0.2	1.07	Ambiguous	1.42	Ambiguous	0.16	Likely Benign	0.895	Likely Pathogenic	-7.77	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	5.75	Benign	0.00	Affected			0.0684	0.5162		-2	-3	7.7	-15.96
c.782A>T	D261V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant D261V is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include premPS, SIFT, and FATHMM, while those that predict a pathogenic effect comprise SGM‑Consensus (Likely Pathogenic), REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the majority of available predictions lean toward pathogenicity, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.284882	Structured	0.422514	Uncertain	0.883	0.264	0.125											-12.138	Likely Pathogenic	0.923	Likely Pathogenic	Ambiguous	1.72	Ambiguous	0.6	-0.68	Ambiguous	0.52	Ambiguous	-0.01	Likely Benign	0.869	Likely Pathogenic	-5.50	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	5.73	Benign	0.08	Tolerated			0.0553	0.4734		-2	-3	7.7	-15.96
c.860A>T	D287V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant D287V is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only premPS; all other evaluated algorithms (SGM‑Consensus, REVEL, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic impact, while FoldX is uncertain and thus not counted as evidence. High‑accuracy methods further support pathogenicity: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. No prediction or stability result is missing or inconclusive. Based on the overwhelming consensus of pathogenic predictions, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.102787	Structured	0.389029	Uncertain	0.912	0.268	0.000											-14.418	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	1.71	Ambiguous	0.4	3.94	Destabilizing	2.83	Destabilizing	0.25	Likely Benign	0.516	Likely Pathogenic	-8.27	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.57	Pathogenic	0.01	Affected			0.0884	0.7788		-2	-3	7.7	-15.96
c.863A>T	D288V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D288V missense variant is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions are provided by REVEL and premPS, whereas the remaining tools—FoldX (uncertain), Rosetta, Foldetta, SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—all indicate a pathogenic effect. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is labeled Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also reports pathogenic. Consequently, the variant is most likely pathogenic based on the aggregate predictions, and this assessment does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.125101	Structured	0.395525	Uncertain	0.873	0.261	0.000											-15.812	Likely Pathogenic	0.981	Likely Pathogenic	Likely Pathogenic	1.74	Ambiguous	0.5	5.44	Destabilizing	3.59	Destabilizing	0.13	Likely Benign	0.481	Likely Benign	-7.14	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.63	Pathogenic	0.05	Affected			0.0838	0.5545		-2	-3	7.7	-15.96
c.911A>T	D304V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D304V missense variant is not reported in ClinVar (ClinVar status: None) and has no entry in gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include Rosetta and premPS, while the majority of tools predict a pathogenic impact: SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Uncertain or inconclusive results come from FoldX, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the preponderance of evidence points to a pathogenic effect for D304V. This conclusion is not contradicted by ClinVar, which currently has no classification for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.352862	Structured	0.285053	Uncertain	0.764	0.271	0.250											-8.280	Likely Pathogenic	0.803	Likely Pathogenic	Ambiguous	1.35	Ambiguous	0.3	0.14	Likely Benign	0.75	Ambiguous	0.35	Likely Benign	0.541	Likely Pathogenic	-6.22	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.81	Pathogenic	0.00	Affected			0.0971	0.6999		-2	-3	7.7	-15.96
c.989A>T	D330V 2D 3DClick to see structure in 3D Viewer AISynGAP1 D330V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL and premPS, whereas a majority of tools predict a pathogenic impact: polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, PROVEAN, and AlphaMissense‑Default. Uncertain predictions from FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized are treated as unavailable. High‑accuracy assessments show that the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. AlphaMissense‑Optimized and Foldetta provide inconclusive results and are therefore not considered evidence. Overall, the preponderance of evidence points to a pathogenic effect for D330V, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.380708	Structured	0.360008	Uncertain	0.805	0.488	0.250											-13.176	Likely Pathogenic	0.950	Likely Pathogenic	Ambiguous	2.06	Destabilizing	0.5	0.57	Ambiguous	1.32	Ambiguous	0.45	Likely Benign	0.428	Likely Benign	-6.40	Deleterious	0.994	Probably Damaging	0.892	Possibly Damaging	0.89	Pathogenic	0.01	Affected			0.0862	0.4633		-2	-3	7.7	-15.96
c.995A>T	D332V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D332V missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Foldetta, and premPS, whereas a majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Uncertain results come from FoldX, Rosetta, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Benign. Overall, the balance of evidence favors a pathogenic classification; this conclusion does not contradict any ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.339168	Structured	0.336528	Uncertain	0.537	0.445	0.375											-13.710	Likely Pathogenic	0.933	Likely Pathogenic	Ambiguous	1.39	Ambiguous	0.1	-0.52	Ambiguous	0.44	Likely Benign	0.50	Likely Benign	0.484	Likely Benign	-7.27	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.21	Pathogenic	0.03	Affected			0.0573	0.4132		-2	-3	7.7	-15.96
c.1181A>T	K394I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K394I missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include premPS, polyPhen‑2 HumVar, and FATHMM, while a majority (seven) predict pathogenicity: SGM‑Consensus (Likely Pathogenic), REVEL, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy methods give mixed results: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) remains Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) is uncertain. No evidence from these tools contradicts the ClinVar status, which is absent. Overall, the preponderance of pathogenic predictions suggests the variant is most likely pathogenic, with no conflict from ClinVar data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.505461	Disordered	0.399336	Uncertain	0.387	0.634	0.625											-9.244	Likely Pathogenic	0.876	Likely Pathogenic	Ambiguous	0.78	Ambiguous	0.2	1.10	Ambiguous	0.94	Ambiguous	0.19	Likely Benign	0.519	Likely Pathogenic	-3.96	Deleterious	0.700	Possibly Damaging	0.403	Benign	4.59	Benign	0.00	Affected			0.1728	0.4123		-2	-3	8.4	-15.01
c.1208A>T	K403I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K403I is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that classify the variant as benign include FoldX, Rosetta, Foldetta, premPS, and FATHMM, while the remaining tools—SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict it to be pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of predictions (nine pathogenic vs. five benign) and the high‑accuracy tools lean toward a pathogenic effect. Thus, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.275179	Structured	0.424920	Uncertain	0.960	0.372	0.000											-15.239	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	0.17	Likely Benign	0.1	-0.46	Likely Benign	-0.15	Likely Benign	0.36	Likely Benign	0.519	Likely Pathogenic	-7.27	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.70	Benign	0.00	Affected			0.1223	0.4141		-2	-3	8.4	-15.01
c.1253A>T	K418I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K418I is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that indicate a benign effect include REVEL, premPS, and FATHMM. In contrast, the majority of tools predict a pathogenic outcome: SGM‑Consensus (Likely Pathogenic), PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX, Rosetta, and Foldetta provide uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic, SGM‑Consensus as Likely Pathogenic, and Foldetta as Uncertain. Overall, the preponderance of evidence points to a pathogenic effect for K418I, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.104810	Structured	0.360134	Uncertain	0.948	0.263	0.000											-14.895	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	0.51	Ambiguous	0.0	0.64	Ambiguous	0.58	Ambiguous	0.27	Likely Benign	0.428	Likely Benign	-7.27	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.32	Benign	0.01	Affected			0.1297	0.2432		-2	-3	8.4	-15.01
c.1325A>T	K442I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K442I missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, and FATHMM. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy assessments are: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign. Overall, the majority of predictions, including the two high‑accuracy pathogenic calls, indicate a pathogenic impact. There is no ClinVar entry to contradict this assessment, so the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.170161	Structured	0.255766	Uncertain	0.912	0.225	0.000											-14.921	Likely Pathogenic	0.965	Likely Pathogenic	Likely Pathogenic	0.16	Likely Benign	0.1	-0.16	Likely Benign	0.00	Likely Benign	0.30	Likely Benign	0.350	Likely Benign	-6.91	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.37	Benign	0.02	Affected			0.0943	0.3073		-2	-3	8.4	-15.01
c.1475A>T	K492I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K492I is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions from premPS and FATHMM; pathogenic predictions from SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain results come from FoldX, Rosetta, and Foldetta. High‑accuracy methods give a pathogenic verdict: AlphaMissense‑Optimized predicts pathogenic; the SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also predicts pathogenic (3/4 votes). Foldetta remains inconclusive. Overall, the majority of evidence points to a pathogenic effect, and this assessment does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.061840	Structured	0.327121	Uncertain	0.947	0.192	0.000											-18.661	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	-0.54	Ambiguous	0.1	-0.59	Ambiguous	-0.57	Ambiguous	0.49	Likely Benign	0.645	Likely Pathogenic	-7.96	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	2.94	Benign	0.00	Affected			0.0875	0.2810		-2	-3	8.4	-15.01
c.1511A>T	K504I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K504I is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess the variant’s effect fall into two groups: benign predictions include REVEL, FoldX, Rosetta, Foldetta, premPS, and AlphaMissense‑Optimized; pathogenic predictions include PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, labels the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus as pathogenic. Because the majority of tools (seven) predict pathogenicity while three high‑accuracy methods provide conflicting evidence, the overall prediction leans toward pathogenic. This assessment does not contradict ClinVar status, as no ClinVar entry exists for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.028107	Structured	0.304984	Uncertain	0.850	0.189	0.000											-12.597	Likely Pathogenic	0.727	Likely Pathogenic	Likely Benign	-0.04	Likely Benign	0.3	-0.36	Likely Benign	-0.20	Likely Benign	0.40	Likely Benign	0.491	Likely Benign	-7.35	Deleterious	0.996	Probably Damaging	0.993	Probably Damaging	-1.49	Pathogenic	0.02	Affected			0.0769	0.2713		-2	-3	8.4	-15.01
c.239A>T	K80I 2D AIThe SynGAP1 missense variant K80I is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, ESM1b, and FATHMM, while those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized remains uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a 2‑vs‑2 tie, and Foldetta data are unavailable. Consequently, the variant’s predicted impact is ambiguous, with an equal split between benign and pathogenic signals and no ClinVar entry to contradict the computational assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.637480	Disordered	0.477530	Uncertain	0.331	0.873	0.500											-5.320	Likely Benign	0.947	Likely Pathogenic	Ambiguous										0.083	Likely Benign	-2.54	Deleterious	0.939	Possibly Damaging	0.164	Benign	3.86	Benign	0.00	Affected			0.1095	0.2981		-2	-3	8.4	-15.01
c.2408A>T	K803I 2D AIThe SynGAP1 K803I missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score. The high‑accuracy AlphaMissense‑Optimized assessment is uncertain, and the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a pathogenic effect, and this conclusion does not contradict the ClinVar status, which currently contains no classification for K803I. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.827927	Disordered	0.733908	Binding	0.349	0.900	0.625											-5.207	Likely Benign	0.894	Likely Pathogenic	Ambiguous										0.196	Likely Benign	-4.06	Deleterious	0.995	Probably Damaging	0.913	Probably Damaging	2.31	Pathogenic	0.00	Affected			0.1425	0.3889		-2	-3	8.4	-15.01
c.3248A>T	K1083I 2D AIThe SynGAP1 missense variant K1083I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Benign, and the Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of a ClinVar entry, so there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.837511	Disordered	0.978906	Binding	0.302	0.893	1.000											-3.207	Likely Benign	0.836	Likely Pathogenic	Ambiguous										0.239	Likely Benign	-1.65	Neutral	0.999	Probably Damaging	0.997	Probably Damaging	4.02	Benign	0.30	Tolerated			0.1394	0.3978		-2	-3	8.4	-15.01
c.3554A>T	K1185I 2D AIThe SynGAP1 missense variant K1185I is listed in ClinVar with no pathogenicity classification (ClinVar status: None) and is present in the gnomAD database (gnomAD ID: 6‑33444589‑A‑T). Prediction tools that agree on a benign effect include REVEL, SIFT, ESM1b, and FATHMM, while those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑vs‑2 split, and Foldetta results are unavailable. Based on the overall pattern of predictions, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which remains unclassified. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.566480	Disordered	0.510264	Binding	0.642	0.638	0.625								6-33444589-A-T	1	6.20e-7	-5.101	Likely Benign	0.990	Likely Pathogenic	Likely Pathogenic										0.215	Likely Benign	-3.42	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	2.62	Benign	0.09	Tolerated	3.82	4	0.1154	0.3108		-3	-2	8.4	-15.01
c.3617A>T	K1206I 2D AIThe SynGAP1 missense variant K1206I is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM‑Consensus as Likely Pathogenic; Foldetta results are not available. Overall, the preponderance of evidence from multiple in silico predictors points to a pathogenic effect for K1206I. This conclusion is not contradicted by ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.585406	Disordered	0.555819	Binding	0.893	0.569	0.375											-13.526	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic										0.302	Likely Benign	-5.65	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.37	Pathogenic	0.01	Affected			0.0816	0.3521		-2	-3	8.4	-15.01
c.3695A>T	K1232I 2D AIThe SynGAP1 K1232I missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—consistently predict a pathogenic impact. The high‑accuracy assessment shows AlphaMissense‑Optimized as uncertain, while the SGM‑Consensus (derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is classified as Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a pathogenic effect; this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.505461	Disordered	0.542907	Binding	0.894	0.535	0.125											-12.225	Likely Pathogenic	0.896	Likely Pathogenic	Ambiguous										0.197	Likely Benign	-5.98	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.08	Pathogenic	0.00	Affected			0.0778	0.3321		-2	-3	8.4	-15.01
c.413A>T	K138I 2D AIThe SynGAP1 missense variant K138I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus also indicates Likely Pathogenic. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of computational evidence points to a pathogenic effect, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.590140	Disordered	0.619482	Binding	0.349	0.901	0.375											-9.366	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic										0.295	Likely Benign	-4.74	Deleterious	0.535	Possibly Damaging	0.259	Benign	3.53	Benign	0.00	Affected			0.1003	0.3054		-2	-3	8.4	-15.01
c.425A>T	K142I 2D AIThe SynGAP1 missense variant K142I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts Pathogenic, and the SGM‑Consensus also indicates Likely Pathogenic. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of computational evidence points to a pathogenic effect, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.461924	Structured	0.558796	Binding	0.374	0.859	0.500											-14.597	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.296	Likely Benign	-4.81	Deleterious	0.700	Possibly Damaging	0.403	Benign	3.44	Benign	0.00	Affected			0.1005	0.3173		-2	-3	8.4	-15.01
c.446A>T	K149I 2D AIThe SynGAP1 missense variant K149I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM‑Consensus as Likely Pathogenic; the Foldetta protein‑folding stability analysis is unavailable. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.562014	Disordered	0.501681	Binding	0.302	0.839	0.625											-14.426	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic										0.305	Likely Benign	-4.72	Deleterious	0.535	Possibly Damaging	0.403	Benign	3.53	Benign	0.00	Affected			0.1477	0.3965		-2	-3	8.4	-15.01
c.686A>T	K229I 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K229I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split assessment: benign predictions come from FoldX, Foldetta, premPS, and FATHMM, whereas pathogenic predictions are returned by SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy methods give a mixed picture: AlphaMissense‑Optimized predicts pathogenic; the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, reports benign. No prediction is inconclusive. Overall, the majority of tools, including the high‑accuracy ones, lean toward pathogenicity, and this does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.179055	Structured	0.310912	Uncertain	0.843	0.306	0.000											-15.276	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	-0.03	Likely Benign	0.1	-0.63	Ambiguous	-0.33	Likely Benign	-0.19	Likely Benign	0.833	Likely Pathogenic	-6.52	Deleterious	0.998	Probably Damaging	0.991	Probably Damaging	5.92	Benign	0.00	Affected			0.1202	0.3711		-2	-3	8.4	-15.01
c.722A>T	K241I 2D 3DClick to see structure in 3D Viewer AISynGAP1 K241I is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include Rosetta, premPS, and FATHMM. Those that predict a damaging effect are REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). FoldX and Foldetta return uncertain results. High‑accuracy methods give a consistent pathogenic signal: AlphaMissense‑Optimized reports pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, while Foldetta remains inconclusive. Overall, the majority of evidence points to a pathogenic effect, and this assessment does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.196879	Structured	0.349250	Uncertain	0.797	0.347	0.000											-14.370	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	1.31	Ambiguous	0.5	0.28	Likely Benign	0.80	Ambiguous	0.41	Likely Benign	0.852	Likely Pathogenic	-6.96	Deleterious	0.985	Probably Damaging	0.704	Possibly Damaging	5.71	Benign	0.01	Affected			0.1176	0.3868		-2	-3	8.4	-15.01
c.998A>T	K333I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K333I missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include FoldX and premPS, whereas the majority of tools (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic impact; Rosetta and Foldetta give uncertain results. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized classifies the variant as pathogenic, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports it as Likely Pathogenic, and Foldetta remains uncertain. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.311707	Structured	0.330781	Uncertain	0.537	0.447	0.500											-14.517	Likely Pathogenic	0.985	Likely Pathogenic	Likely Pathogenic	0.30	Likely Benign	0.0	0.95	Ambiguous	0.63	Ambiguous	0.43	Likely Benign	0.544	Likely Pathogenic	-6.49	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.89	Pathogenic	0.03	Affected			0.0931	0.3521		-2	-3	8.4	-15.01
c.1082A>T	Q361L 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant Q361L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, Rosetta, Foldetta, premPS, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized; pathogenic predictions arise from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of tools (8 benign vs 5 pathogenic) favor a benign effect, and this consensus does not contradict the absence of a ClinVar classification. Thus, the variant is most likely benign based on current predictions, with no conflict with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.305330	Structured	0.427593	Uncertain	0.945	0.534	0.250											-10.678	Likely Pathogenic	0.238	Likely Benign	Likely Benign	0.12	Likely Benign	0.1	0.46	Likely Benign	0.29	Likely Benign	0.21	Likely Benign	0.406	Likely Benign	-3.95	Deleterious	0.987	Probably Damaging	0.953	Probably Damaging	1.71	Pathogenic	0.06	Tolerated			0.0720	0.5213		-2	-2	7.3	-14.97
c.1220A>T	Q407L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q407L is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, premPS, FATHMM, and AlphaMissense‑Optimized. Those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b. Four tools are uncertain (AlphaMissense‑Default, FoldX, Rosetta, Foldetta). High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, more tools predict pathogenicity than benign, and the high‑accuracy consensus leans pathogenic. Therefore, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.109221	Structured	0.382522	Uncertain	0.916	0.271	0.000											-12.730	Likely Pathogenic	0.558	Ambiguous	Likely Benign	-0.65	Ambiguous	0.2	-0.69	Ambiguous	-0.67	Ambiguous	0.35	Likely Benign	0.359	Likely Benign	-6.32	Deleterious	0.939	Possibly Damaging	0.838	Possibly Damaging	3.91	Benign	0.02	Affected			0.0585	0.4977		-2	-2	7.3	-14.97
c.1367A>T	Q456L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q456L is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Rosetta, premPS, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. Tools with uncertain or inconclusive results are FoldX, Foldetta, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of predictions (six benign vs. four pathogenic) lean toward a benign interpretation, with no evidence of contradiction with the ClinVar status. Thus, the variant is most likely benign based on current computational predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.170161	Structured	0.302348	Uncertain	0.939	0.164	0.000											-10.272	Likely Pathogenic	0.492	Ambiguous	Likely Benign	-0.88	Ambiguous	0.1	-0.30	Likely Benign	-0.59	Ambiguous	0.28	Likely Benign	0.347	Likely Benign	-6.65	Deleterious	0.987	Probably Damaging	0.914	Probably Damaging	3.49	Benign	0.36	Tolerated			0.0554	0.4317		-2	-2	7.3	-14.97
c.1508A>T	Q503L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q503L is not reported in ClinVar and has no entries in gnomAD. Prediction tools that agree on a benign effect include AlphaMissense‑Default, AlphaMissense‑Optimized, Foldetta, premPS, Rosetta, and polyPhen‑2 (HumVar). Those that predict a pathogenic effect are SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv), SIFT, ESM1b, and FATHMM; FoldX is uncertain and therefore not counted. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta as benign. Overall, the majority of tools (seven versus six) predict pathogenicity, and the high‑accuracy trio is split but leans toward pathogenic. Thus, the variant is most likely pathogenic based on current predictions, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.040537	Structured	0.322935	Uncertain	0.848	0.168	0.000											-8.203	Likely Pathogenic	0.261	Likely Benign	Likely Benign	-0.56	Ambiguous	0.2	-0.07	Likely Benign	-0.32	Likely Benign	0.24	Likely Benign	0.711	Likely Pathogenic	-6.29	Deleterious	0.911	Possibly Damaging	0.369	Benign	-1.52	Pathogenic	0.05	Affected			0.0715	0.3578		-2	-2	7.3	-14.97
c.1619A>T	Q540L 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant Q540L has no ClinVar entry and is not reported in gnomAD. Functional prediction tools show a split: benign calls come from Rosetta, Foldetta, premPS, and SIFT, while pathogenic calls are made by REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX is uncertain and therefore not considered. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is Likely Pathogenic, whereas Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts benign. Overall, the majority of evidence points to a pathogenic impact for Q540L, and this conclusion does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.085092	Structured	0.029522	Uncertain	0.958	0.371	0.000											-14.266	Likely Pathogenic	0.965	Likely Pathogenic	Likely Pathogenic	-0.71	Ambiguous	0.1	0.44	Likely Benign	-0.14	Likely Benign	0.50	Likely Benign	0.756	Likely Pathogenic	-6.96	Deleterious	0.994	Probably Damaging	0.977	Probably Damaging	-1.06	Pathogenic	0.08	Tolerated			0.0654	0.3601		-2	-2	7.3	-14.97
c.164A>T	Q55L 2D AIThe SynGAP1 missense variant Q55L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports the variant as likely benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar annotation (none exists). Thus, the variant is most likely benign based on current predictive data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.332115	Structured	0.470108	Uncertain	0.461	0.657	0.000											-5.823	Likely Benign	0.844	Likely Pathogenic	Ambiguous										0.173	Likely Benign	-1.99	Neutral	0.273	Benign	0.275	Benign	3.83	Benign	0.00	Affected			0.0776	0.5982		-2	-2	7.3	-14.97
c.1835A>T	Q612L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q612L is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include FoldX, Rosetta, Foldetta, premPS, and SIFT, whereas those that predict a pathogenic effect are REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain (unavailable), SGM Consensus as likely pathogenic, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta) as benign. Overall, the majority of conventional tools lean toward pathogenicity, and the SGM Consensus supports this, while the high‑accuracy Foldetta result is contradictory. Thus, the variant is most likely pathogenic based on the prevailing predictions, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.275179	Structured	0.203988	Uncertain	0.822	0.263	0.000											-12.076	Likely Pathogenic	0.799	Likely Pathogenic	Ambiguous	-0.12	Likely Benign	0.1	0.12	Likely Benign	0.00	Likely Benign	0.44	Likely Benign	0.730	Likely Pathogenic	-6.84	Deleterious	0.971	Probably Damaging	0.954	Probably Damaging	-1.33	Pathogenic	0.08	Tolerated			0.0763	0.4756		-2	-2	7.3	-14.97
c.1853A>T	Q618L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q618L is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, SIFT, and polyPhen‑2 HumVar, while those that predict a pathogenic effect are SGM‑Consensus (Likely Pathogenic), PROVEAN, polyPhen‑2 HumDiv, ESM1b, and FATHMM. AlphaMissense‑Default is uncertain, whereas AlphaMissense‑Optimized predicts benign. High‑accuracy methods give the following results: AlphaMissense‑Optimized – benign; SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) – Likely Pathogenic; Foldetta – benign. Overall, the majority of tools (nine benign vs. five pathogenic) predict a benign impact. Thus, the variant is most likely benign based on current predictions, and this assessment does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.175930	Structured	0.138725	Uncertain	0.904	0.240	0.000											-8.561	Likely Pathogenic	0.423	Ambiguous	Likely Benign	-0.07	Likely Benign	0.1	0.20	Likely Benign	0.07	Likely Benign	0.31	Likely Benign	0.479	Likely Benign	-3.94	Deleterious	0.712	Possibly Damaging	0.268	Benign	-1.28	Pathogenic	0.09	Tolerated			0.0612	0.4146		-2	-2	7.3	-14.97
c.1892A>T	Q631L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q631L is not reported in ClinVar (ClinVar status: None) and has no entry in gnomAD (gnomAD status: None). Prediction tools that agree on a benign effect include FATHMM and Foldetta, whereas the majority of tools predict a pathogenic impact: SGM‑Consensus (likely pathogenic), REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely pathogenic, and Foldetta as benign; these results are reported but not used as definitive evidence when inconclusive. Overall, the preponderance of evidence from consensus and individual predictors indicates a pathogenic effect for Q631L. This conclusion does not contradict ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.041405	Structured	0.038963	Uncertain	0.948	0.230	0.000											-14.727	Likely Pathogenic	0.901	Likely Pathogenic	Ambiguous	-1.23	Ambiguous	0.0	0.95	Ambiguous	-0.14	Likely Benign	0.51	Ambiguous	0.619	Likely Pathogenic	-6.97	Deleterious	0.982	Probably Damaging	0.954	Probably Damaging	2.85	Benign	0.05	Affected			0.0627	0.3150		-2	-2	7.3	-14.97
c.1982A>T	Q661L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q661L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect comprise SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain, so it is not used as evidence. Overall, the majority of predictions support a pathogenic impact, and this is consistent with the lack of ClinVar annotation. Therefore, the variant is most likely pathogenic, with no contradiction from ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.048328	Structured	0.117089	Uncertain	0.924	0.309	0.000											-9.003	Likely Pathogenic	0.613	Likely Pathogenic	Likely Benign	-0.19	Likely Benign	0.1	-1.12	Ambiguous	-0.66	Ambiguous	0.36	Likely Benign	0.391	Likely Benign	-5.11	Deleterious	0.976	Probably Damaging	0.567	Possibly Damaging	3.49	Benign	0.02	Affected			0.0834	0.4675		-2	-2	7.3	-14.97
c.1985A>T	Q662L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q662L is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, SIFT, AlphaMissense‑Default, AlphaMissense‑Optimized, polyPhen2_HumVar, and FATHMM. Tools that predict a pathogenic effect are PROVEAN, polyPhen2_HumDiv, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign and Foldetta as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic). Overall, the majority of evidence supports a benign impact. This conclusion is consistent with the lack of ClinVar annotation and gnomAD presence, so there is no contradiction with existing database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.046336	Structured	0.103446	Uncertain	0.932	0.323	0.000											-10.291	Likely Pathogenic	0.300	Likely Benign	Likely Benign	0.04	Likely Benign	0.0	0.12	Likely Benign	0.08	Likely Benign	0.17	Likely Benign	0.186	Likely Benign	-4.09	Deleterious	0.699	Possibly Damaging	0.057	Benign	3.42	Benign	0.10	Tolerated			0.1070	0.5255		-2	-2	7.3	-14.97
c.2105A>T	Q702L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q702L is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that classify the variant as benign include REVEL, FoldX, Rosetta, Foldetta, premPS, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict pathogenicity are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑vs‑2 split. Overall, the balance of evidence leans toward a benign effect. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.074921	Structured	0.397258	Uncertain	0.907	0.345	0.000											-9.954	Likely Pathogenic	0.149	Likely Benign	Likely Benign	-0.13	Likely Benign	0.0	0.09	Likely Benign	-0.02	Likely Benign	0.16	Likely Benign	0.392	Likely Benign	-5.66	Deleterious	0.939	Possibly Damaging	0.838	Possibly Damaging	3.42	Benign	0.00	Affected			0.0584	0.3628		-2	-2	7.3	-14.97
c.2192A>T	Q731L 2D AIThe SynGAP1 missense variant Q731L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv indicates a pathogenic effect, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign and the SGM‑Consensus is Likely Benign; Foldetta results are not available. Overall, the preponderance of evidence points to a benign impact for Q731L, and this conclusion is not contradicted by any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.750527	Disordered	0.415202	Uncertain	0.507	0.654	0.750											-4.251	Likely Benign	0.110	Likely Benign	Likely Benign										0.161	Likely Benign	-1.27	Neutral	0.825	Possibly Damaging	0.270	Benign	2.75	Benign	0.12	Tolerated			0.0879	0.5694		-2	-2	7.3	-14.97
c.2198A>T	Q733L 2D AIThe SynGAP1 missense variant Q733L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv indicates a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also reports Likely Benign. No Foldetta stability analysis is available, so it does not influence the assessment. Overall, the preponderance of evidence points to a benign effect, and this conclusion is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.874069	Disordered	0.410831	Uncertain	0.331	0.686	0.875											-3.465	Likely Benign	0.093	Likely Benign	Likely Benign										0.128	Likely Benign	-2.04	Neutral	0.905	Possibly Damaging	0.408	Benign	2.55	Benign	1.00	Tolerated			0.0736	0.4291		-2	-2	7.3	-14.97
c.2210A>T	Q737L 2D AIThe SynGAP1 missense variant Q737L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is “Likely Benign”). In contrast, the two polyPhen‑2 implementations (HumDiv and HumVar) predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is also likely benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence indicates that the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.889439	Disordered	0.425743	Uncertain	0.323	0.803	0.875											-2.789	Likely Benign	0.085	Likely Benign	Likely Benign										0.053	Likely Benign	-2.44	Neutral	0.959	Probably Damaging	0.721	Possibly Damaging	2.80	Benign	1.00	Tolerated			0.0958	0.5494		-2	-2	7.3	-14.97
c.2231A>T	Q744L 2D AIThe SynGAP1 missense variant Q744L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta results are not available for this variant. Overall, the preponderance of evidence points to a benign effect. This conclusion is consistent with the lack of ClinVar annotation; there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.852992	Disordered	0.540428	Binding	0.316	0.866	0.875											-3.724	Likely Benign	0.100	Likely Benign	Likely Benign										0.052	Likely Benign	-1.96	Neutral	0.425	Benign	0.158	Benign	2.70	Benign	0.02	Affected			0.0813	0.4731		-2	-2	7.3	-14.97
c.2267A>T	Q756L 2D AIThe SynGAP1 missense variant Q756L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is labeled “Likely Benign”). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact for Q756L, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.458154	Structured	0.806299	Binding	0.340	0.866	0.250											-3.697	Likely Benign	0.339	Likely Benign	Likely Benign										0.274	Likely Benign	-1.95	Neutral	0.994	Probably Damaging	0.988	Probably Damaging	1.56	Pathogenic	0.08	Tolerated			0.0797	0.5700		-2	-2	7.3	-14.97
c.2309A>T	Q770L 2D AIThe SynGAP1 missense variant Q770L is not reported in ClinVar and is absent from gnomAD, indicating no known population frequency data. Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Benign. No Foldetta stability prediction is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect for Q770L, and this conclusion is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.436924	Structured	0.923732	Binding	0.328	0.887	0.250											-5.524	Likely Benign	0.521	Ambiguous	Likely Benign										0.197	Likely Benign	-2.17	Neutral	0.095	Benign	0.030	Benign	4.14	Benign	0.01	Affected			0.0776	0.6230		-2	-2	7.3	-14.97
c.2495A>T	Q832L 2D AIThe SynGAP1 missense variant Q832L is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as benign. Only polyPhen‑2 HumDiv predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign. Foldetta results are unavailable. Overall, the preponderance of evidence indicates that the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.720929	Disordered	0.619913	Binding	0.290	0.877	0.375											-2.299	Likely Benign	0.190	Likely Benign	Likely Benign										0.090	Likely Benign	-0.58	Neutral	0.811	Possibly Damaging	0.424	Benign	2.84	Benign	1.00	Tolerated			0.0676	0.4852		-2	-2	7.3	-14.97
c.2540A>T	Q847L 2D AIThe SynGAP1 missense variant Q847L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default—predict a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, SGM‑Consensus as Likely Pathogenic, and the Foldetta stability analysis is unavailable. Overall, the majority of predictions lean toward pathogenicity, and this conclusion does not contradict any existing ClinVar annotation, as none is available. Thus, the variant is most likely pathogenic based on the current computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.653063	Disordered	0.577677	Binding	0.282	0.818	0.500											-6.966	Likely Benign	0.625	Likely Pathogenic	Likely Benign										0.326	Likely Benign	-4.52	Deleterious	0.818	Possibly Damaging	0.637	Possibly Damaging	2.33	Pathogenic	0.00	Affected			0.0701	0.5132		-2	-2	7.3	-14.97
c.2621A>T	Q874L 2D AIThe SynGAP1 missense variant Q874L is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic). Foldetta results are unavailable. Overall, the majority of predictions (five pathogenic vs four benign) lean toward pathogenicity. Thus, the variant is most likely pathogenic based on current computational evidence, and this assessment does not contradict any ClinVar status because the variant has not been reported there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.490133	Structured	0.635258	Binding	0.289	0.873	0.250											-6.084	Likely Benign	0.608	Likely Pathogenic	Likely Benign										0.199	Likely Benign	-3.39	Deleterious	0.985	Probably Damaging	0.982	Probably Damaging	2.67	Benign	0.00	Affected			0.0828	0.6595		-2	-2	7.3	-14.97
c.2678A>T	Q893L 2D AIThe SynGAP1 missense variant Q893L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of all available predictions is benign, and this conclusion does not contradict any ClinVar annotation (none present). Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.754692	Disordered	0.447267	Uncertain	0.310	0.925	0.750											-1.964	Likely Benign	0.204	Likely Benign	Likely Benign										0.078	Likely Benign	-1.92	Neutral	0.451	Benign	0.209	Benign	2.82	Benign	1.00	Tolerated			0.0904	0.5643		-2	-2	7.3	-14.97
c.2723A>T	Q908L 2D AIThe SynGAP1 missense variant Q908L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while polyPhen‑2 (HumDiv and HumVar) and SIFT uniformly predict a pathogenic impact. AlphaMissense‑Default remains uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, SGM‑Consensus is Likely Benign, and Foldetta results are unavailable. Based on the collective evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.608892	Disordered	0.678728	Binding	0.275	0.917	0.250											-3.589	Likely Benign	0.420	Ambiguous	Likely Benign										0.193	Likely Benign	-1.40	Neutral	0.985	Probably Damaging	0.982	Probably Damaging	2.53	Benign	0.05	Affected			0.0706	0.5655		-2	-2	7.3	-14.97
c.2756A>T	Q919L 2D AIThe SynGAP1 missense variant Q919L is reported in gnomAD (ID 6‑33443308‑A‑T) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; pathogenic predictions come from polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as “Likely Benign.” High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) also indicates benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar status, as none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.618285	Disordered	0.911223	Binding	0.299	0.841	0.250								6-33443308-A-T	1	6.20e-7	-4.492	Likely Benign	0.252	Likely Benign	Likely Benign										0.175	Likely Benign	-2.13	Neutral	0.891	Possibly Damaging	0.596	Possibly Damaging	2.40	Pathogenic	0.04	Affected	4.32	4	0.0771	0.6454		-2	-2	7.3	-14.97
c.2759A>T	Q920L 2D AIThe SynGAP1 missense variant Q920L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign; Foldetta results are not available. Based on the collective evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.699094	Disordered	0.927260	Binding	0.306	0.845	0.250											-4.048	Likely Benign	0.280	Likely Benign	Likely Benign										0.181	Likely Benign	-2.36	Neutral	0.891	Possibly Damaging	0.596	Possibly Damaging	2.60	Benign	0.00	Affected			0.0774	0.5995		-2	-2	7.3	-14.97
c.2783A>T	Q928L 2D AIThe SynGAP1 missense variant Q928L has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of other in‑silico predictors (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default) and the SGM‑Consensus score (Likely Pathogenic) all indicate a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the SGM‑Consensus outcome, the variant is most likely pathogenic. This conclusion is not contradicted by ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.497853	Structured	0.986260	Binding	0.324	0.852	0.250											-6.237	Likely Benign	0.919	Likely Pathogenic	Ambiguous										0.373	Likely Benign	-4.57	Deleterious	0.994	Probably Damaging	0.988	Probably Damaging	1.56	Pathogenic	0.00	Affected			0.0757	0.6091		-2	-2	7.3	-14.97
c.3062A>T	Q1021L 2D AIThe SynGAP1 missense variant Q1021L is not reported in ClinVar (ClinVar status: not listed) and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑vs‑2 split, and Foldetta results are unavailable. Overall, the majority of predictions (5 pathogenic vs. 4 benign) indicate that the variant is most likely pathogenic. This conclusion does not contradict ClinVar status, as the variant has no existing ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.899122	Disordered	0.979641	Binding	0.326	0.763	0.500											-5.780	Likely Benign	0.678	Likely Pathogenic	Likely Benign										0.226	Likely Benign	-3.36	Deleterious	0.985	Probably Damaging	0.982	Probably Damaging	2.58	Benign	0.01	Affected			0.0688	0.5039		-2	-2	7.3	-14.97
c.3074A>T	Q1025L 2D AIThe SynGAP1 missense variant Q1025L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while those that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus also indicates Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of computational evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.879233	Disordered	0.993410	Binding	0.363	0.746	0.500											-6.460	Likely Benign	0.463	Ambiguous	Likely Benign										0.117	Likely Benign	-2.48	Neutral	0.901	Possibly Damaging	0.534	Possibly Damaging	2.70	Benign	0.05	Affected			0.0798	0.5497		-2	-2	7.3	-14.97
c.3086A>T	Q1029L 2D AIThe SynGAP1 missense variant Q1029L is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include REVEL, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, favors a benign outcome (2 benign vs. 1 pathogenic, with one uncertain). AlphaMissense‑Default remains uncertain, and Foldetta results are unavailable. High‑accuracy predictions therefore point to a benign impact: AlphaMissense‑Optimized is benign, SGM Consensus is benign, and no Foldetta data are available. Overall, the computational evidence indicates that the variant is most likely benign, and this assessment does not contradict any ClinVar status because no ClinVar claim exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.852992	Disordered	0.995643	Binding	0.375	0.734	0.500											-3.984	Likely Benign	0.364	Ambiguous	Likely Benign										0.067	Likely Benign	-2.65	Deleterious	0.891	Possibly Damaging	0.587	Possibly Damaging	2.70	Benign	0.16	Tolerated			0.0685	0.5866		-2	-2	7.3	-14.97
c.3107A>T	Q1036L 2D AIThe SynGAP1 missense variant Q1036L is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN and SIFT, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also favors a benign outcome, with two benign votes versus one pathogenic and one uncertain. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.948786	Disordered	0.987955	Binding	0.275	0.765	0.625											-4.389	Likely Benign	0.435	Ambiguous	Likely Benign										0.092	Likely Benign	-2.92	Deleterious	0.152	Benign	0.045	Benign	2.52	Benign	0.01	Affected			0.1069	0.5996		-2	-2	7.3	-14.97
c.3125A>T	Q1042L 2D AIThe SynGAP1 missense variant Q1042L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.969315	Disordered	0.959333	Binding	0.310	0.846	0.625											-3.796	Likely Benign	0.203	Likely Benign	Likely Benign										0.338	Likely Benign	-2.47	Neutral	0.369	Benign	0.120	Benign	5.47	Benign	0.05	Affected			0.1469	0.6276		-2	-2	7.3	-14.97
c.3191A>T	Q1064L 2D AIThe SynGAP1 missense variant Q1064L is not reported in ClinVar and is absent from gnomAD, indicating no documented allele frequency data. Functional prediction tools uniformly classify the variant as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a benign effect. No tool in the dataset indicates pathogenicity. High‑accuracy assessments corroborate this benign prediction: AlphaMissense‑Optimized reports benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a “Likely Benign” verdict. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, is not available for this variant. Overall, the consensus of all available predictions strongly supports a benign classification, with no contradiction to ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.978316	Disordered	0.953106	Binding	0.378	0.914	0.875											-3.492	Likely Benign	0.099	Likely Benign	Likely Benign										0.133	Likely Benign	-1.16	Neutral	0.224	Benign	0.091	Benign	4.20	Benign	0.13	Tolerated			0.1817	0.5485		-2	-2	7.3	-14.97
c.3206A>T	Q1069L 2D AIThe SynGAP1 missense variant Q1069L is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. The high‑accuracy consensus methods corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Overall, the variant is most likely benign based on the collective predictions, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.943310	Disordered	0.981477	Binding	0.333	0.906	0.875											-4.278	Likely Benign	0.141	Likely Benign	Likely Benign										0.104	Likely Benign	-0.96	Neutral	0.003	Benign	0.008	Benign	2.83	Benign	0.10	Tolerated			0.0936	0.6624		-2	-2	7.3	-14.97
c.3221A>T	Q1074L 2D AIThe SynGAP1 missense variant Q1074L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv indicates a pathogenic effect, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also reports Likely Benign. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the preponderance of evidence points to a benign impact, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.930790	Disordered	0.987006	Binding	0.339	0.897	0.750											-3.561	Likely Benign	0.259	Likely Benign	Likely Benign										0.118	Likely Benign	-1.29	Neutral	0.625	Possibly Damaging	0.266	Benign	2.68	Benign	1.00	Tolerated			0.0840	0.6293		-2	-2	7.3	-14.97
c.3224A>T	Q1075L 2D AIThe SynGAP1 missense variant Q1075L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only two tools, polyPhen‑2 HumDiv and HumVar, predict pathogenic. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy methods confirm this: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the majority of evidence supports a benign impact for Q1075L, and this conclusion is consistent with the absence of a ClinVar assertion. The variant is most likely benign based on predictions, and there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.922952	Disordered	0.988305	Binding	0.354	0.894	0.750											-3.976	Likely Benign	0.209	Likely Benign	Likely Benign										0.128	Likely Benign	-2.10	Neutral	0.985	Probably Damaging	0.973	Probably Damaging	2.72	Benign	0.15	Tolerated			0.0888	0.6454		-2	-2	7.3	-14.97
c.3245A>T	Q1082L 2D AIThe SynGAP1 missense variant Q1082L is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. The high‑accuracy consensus methods corroborate this: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta results are unavailable. Overall, the variant is most likely benign, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.819762	Disordered	0.979325	Binding	0.347	0.896	0.875											-3.284	Likely Benign	0.171	Likely Benign	Likely Benign										0.097	Likely Benign	-1.30	Neutral	0.224	Benign	0.058	Benign	4.12	Benign	1.00	Tolerated			0.0979	0.6824		-2	-2	7.3	-14.97
c.3278A>T	Q1093L 2D AIThe SynGAP1 missense variant Q1093L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Based on the preponderance of evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.919029	Disordered	0.983312	Binding	0.351	0.886	1.000											-3.242	Likely Benign	0.165	Likely Benign	Likely Benign										0.055	Likely Benign	-1.10	Neutral	0.224	Benign	0.091	Benign	2.72	Benign	0.03	Affected			0.0899	0.6837		-2	-2	7.3	-14.97
c.3317A>T	Q1106L 2D AIThe SynGAP1 missense variant Q1106L is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 benign vs. 2 pathogenic). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of predictions (five pathogenic vs. four benign) lean toward a pathogenic impact. This assessment does not contradict ClinVar status, as the variant is currently unreported in that database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.885302	Disordered	0.952043	Binding	0.382	0.870	0.875											-4.219	Likely Benign	0.171	Likely Benign	Likely Benign										0.169	Likely Benign	-4.46	Deleterious	0.985	Probably Damaging	0.973	Probably Damaging	1.77	Pathogenic	0.05	Affected			0.0833	0.6282		-2	-2	7.3	-14.97
c.3320A>T	Q1107L 2D AIThe SynGAP1 missense variant Q1107L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. In contrast, PROVEAN and SIFT predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign and the SGM‑Consensus is Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.876521	Disordered	0.951017	Binding	0.393	0.880	0.875											-3.785	Likely Benign	0.116	Likely Benign	Likely Benign										0.119	Likely Benign	-3.27	Deleterious	0.006	Benign	0.004	Benign	2.53	Benign	0.01	Affected			0.0820	0.6447		-2	-2	7.3	-14.97
c.3407A>T	Q1136L 2D AIThe SynGAP1 missense variant Q1136L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly classify the variant as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate a benign effect. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of all available predictions is benign, and this is consistent with the lack of ClinVar evidence; there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.903857	Disordered	0.775584	Binding	0.321	0.884	0.875											-6.020	Likely Benign	0.203	Likely Benign	Likely Benign										0.242	Likely Benign	-2.42	Neutral	0.005	Benign	0.026	Benign	5.44	Benign	0.23	Tolerated			0.0861	0.6395		-2	-2	7.3	-14.97
c.3416A>T	Q1139L 2D AIThe SynGAP1 missense variant Q1139L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. In contrast, PROVEAN and SIFT predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign and the SGM‑Consensus is Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.908098	Disordered	0.721191	Binding	0.313	0.866	1.000											-1.689	Likely Benign	0.153	Likely Benign	Likely Benign										0.472	Likely Benign	-3.75	Deleterious	0.224	Benign	0.237	Benign	5.30	Benign	0.00	Affected			0.0745	0.5599		-2	-2	7.3	-14.97
c.344A>T	Q115L 2D AIThe SynGAP1 missense variant Q115L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only two tools, polyPhen‑2 HumDiv and HumVar, predict a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign effect for Q115L, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.784345	Disordered	0.657256	Binding	0.327	0.878	0.750											-3.281	Likely Benign	0.179	Likely Benign	Likely Benign										0.123	Likely Benign	-1.25	Neutral	0.967	Probably Damaging	0.901	Possibly Damaging	4.10	Benign	0.10	Tolerated			0.0710	0.5452		-2	-2	7.3	-14.97
c.3677A>T	Q1226L 2D AIThe SynGAP1 missense variant Q1226L is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—consistently predict a pathogenic impact. High‑accuracy assessments further support a deleterious interpretation: the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Pathogenic,” AlphaMissense‑Optimized is classified as “Uncertain,” and Foldetta’s protein‑folding stability analysis is unavailable. Taken together, the preponderance of evidence points to a pathogenic effect for Q1226L. This conclusion is not contradicted by ClinVar status, as the variant is currently unreported in that database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.529623	Disordered	0.432206	Uncertain	0.850	0.547	0.250											-11.122	Likely Pathogenic	0.879	Likely Pathogenic	Ambiguous										0.353	Likely Benign	-5.62	Deleterious	0.994	Probably Damaging	0.988	Probably Damaging	1.77	Pathogenic	0.00	Affected			0.0493	0.4282		-2	-2	7.3	-14.97
c.3686A>T	Q1229L 2D AIThe SynGAP1 missense variant Q1229L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into three groups: benign predictions come from REVEL, SIFT, and AlphaMissense‑Optimized; pathogenic predictions arise from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM; the remaining tools (ESM1b and AlphaMissense‑Default) are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, while the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta data are unavailable. Overall, the majority of conventional predictors favor a pathogenic effect, whereas the single high‑accuracy tool suggests benign. Given the lack of ClinVar evidence, the variant is most likely pathogenic according to the collective predictions, with no contradiction to existing clinical annotations. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.490133	Structured	0.466729	Uncertain	0.865	0.544	0.375											-7.366	In-Between	0.496	Ambiguous	Likely Benign										0.349	Likely Benign	-4.60	Deleterious	0.994	Probably Damaging	0.988	Probably Damaging	1.77	Pathogenic	0.09	Tolerated			0.0541	0.4253		-2	-2	7.3	-14.97
c.3707A>T	Q1236L 2D AIThe SynGAP1 missense variant Q1236L is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT; AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts benign, while Foldetta results are unavailable. Overall, the majority of high‑confidence predictions lean toward a benign impact, and there is no conflict with ClinVar status. Thus, the variant is most likely benign based on current computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.680603	Disordered	0.567914	Binding	0.883	0.537	0.125											-6.682	Likely Benign	0.409	Ambiguous	Likely Benign										0.362	Likely Benign	-4.51	Deleterious	0.994	Probably Damaging	0.988	Probably Damaging	2.66	Benign	0.00	Affected			0.0507	0.3805		-2	-2	7.3	-14.97
c.3713A>T	Q1238L 2D AIThe SynGAP1 missense variant Q1238L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated predictors—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN)—classify the variant as pathogenic. AlphaMissense‑Optimized is uncertain, providing no definitive direction. High‑accuracy assessments show the SGM‑Consensus as “Likely Pathogenic,” while AlphaMissense‑Optimized remains uncertain and Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.562014	Disordered	0.548882	Binding	0.855	0.545	0.250											-14.299	Likely Pathogenic	0.876	Likely Pathogenic	Ambiguous										0.353	Likely Benign	-4.89	Deleterious	0.994	Probably Damaging	0.988	Probably Damaging	2.31	Pathogenic	0.01	Affected			0.0543	0.3744		-2	-2	7.3	-14.97
c.3728A>T	Q1243L 2D AIThe SynGAP1 missense variant Q1243L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact for this variant, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.545602	Disordered	0.433693	Uncertain	0.887	0.551	0.500											-6.092	Likely Benign	0.092	Likely Benign	Likely Benign										0.168	Likely Benign	-4.00	Deleterious	0.912	Possibly Damaging	0.629	Possibly Damaging	2.65	Benign	0.02	Affected			0.0541	0.3364		-2	-2	7.3	-14.97
c.3749A>T	Q1250L 2D AIThe SynGAP1 missense variant Q1250L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions (REVEL, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus “Likely Benign”) and pathogenic predictions (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT). High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized scores the variant as benign, and the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates “Likely Benign.” No Foldetta stability analysis is available for this residue. Overall, the majority of evidence points to a benign effect, and this conclusion is consistent with the absence of a ClinVar pathogenic classification. Thus, the variant is most likely benign, and this assessment does not contradict ClinVar, which contains no pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.759478	Disordered	0.360484	Uncertain	0.881	0.554	0.750											-4.409	Likely Benign	0.126	Likely Benign	Likely Benign										0.092	Likely Benign	-3.49	Deleterious	0.994	Probably Damaging	0.988	Probably Damaging	2.65	Benign	0.02	Affected			0.0613	0.3946		-2	-2	7.3	-14.97
c.3752A>T	Q1251L 2D AIThe SynGAP1 missense variant Q1251L is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized, whereas a majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b) predict a pathogenic impact; AlphaMissense‑Default remains uncertain. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized remains benign, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—favors pathogenicity. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the balance of evidence points to a pathogenic effect, and this conclusion does not contradict the ClinVar status, which currently contains no classification for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.771762	Disordered	0.363872	Uncertain	0.869	0.551	0.875											-10.298	Likely Pathogenic	0.412	Ambiguous	Likely Benign										0.279	Likely Benign	-4.71	Deleterious	0.994	Probably Damaging	0.988	Probably Damaging	2.58	Benign	0.00	Affected			0.0626	0.4605		-2	-2	7.3	-14.97
c.3755A>T	Q1252L 2D AIThe SynGAP1 missense variant Q1252L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus—predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta results are unavailable. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.759478	Disordered	0.371411	Uncertain	0.850	0.544	0.875											-8.110	Likely Pathogenic	0.833	Likely Pathogenic	Ambiguous										0.295	Likely Benign	-5.62	Deleterious	0.994	Probably Damaging	0.988	Probably Damaging	1.97	Pathogenic	0.00	Affected			0.0593	0.3689		-2	-2	7.3	-14.97
c.3773A>T	Q1258L 2D AIThe SynGAP1 missense variant Q1258L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: REVEL scores the variant as benign, whereas PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default all predict pathogenicity. Grouping by consensus, the majority of tools (seven) predict pathogenic, while only one tool (REVEL) predicts benign. High‑accuracy assessments further support a deleterious effect: the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, labels the variant as Likely Pathogenic; AlphaMissense‑Optimized remains uncertain, and Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the SGM‑Consensus outcome, the variant is most likely pathogenic. This conclusion aligns with the lack of ClinVar annotation and gnomAD absence, indicating no conflicting evidence from population databases. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.486429	Structured	0.525814	Binding	0.859	0.577	0.250											-10.302	Likely Pathogenic	0.895	Likely Pathogenic	Ambiguous										0.341	Likely Benign	-5.55	Deleterious	0.994	Probably Damaging	0.988	Probably Damaging	1.97	Pathogenic	0.00	Affected			0.0448	0.4137		-2	-2	7.3	-14.97
c.3884A>T	Q1295L 2D AIThe SynGAP1 missense variant Q1295L is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts pathogenic. Foldetta results are unavailable. Overall, the majority of evidence points to a pathogenic impact for Q1295L, and this conclusion does not contradict any ClinVar annotation because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.852992	Disordered	0.892719	Binding	0.499	0.801	0.625											-2.862	Likely Benign	0.348	Ambiguous	Likely Benign										0.379	Likely Benign	-5.63	Deleterious	0.925	Possibly Damaging	0.932	Probably Damaging	2.25	Pathogenic	0.00	Affected			0.0810	0.5672		-2	-2	7.3	-14.97
c.3893A>T	Q1298L 2D AIThe SynGAP1 missense variant Q1298L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. In contrast, PROVEAN and SIFT predict a pathogenic impact. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign outcome. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not conflict with the absence of a ClinVar assertion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.823549	Disordered	0.895297	Binding	0.410	0.821	0.750											-2.251	Likely Benign	0.147	Likely Benign	Likely Benign										0.221	Likely Benign	-3.04	Deleterious	0.224	Benign	0.078	Benign	2.79	Benign	0.04	Affected			0.0667	0.4164		-2	-2	7.3	-14.97
c.389A>T	Q130L 2D AIThe SynGAP1 missense variant Q130L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect for Q130L, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.509769	Disordered	0.718853	Binding	0.306	0.885	0.375											-3.643	Likely Benign	0.278	Likely Benign	Likely Benign										0.167	Likely Benign	-1.63	Neutral	0.967	Probably Damaging	0.901	Possibly Damaging	4.11	Benign	0.02	Affected			0.0975	0.5286		-2	-2	7.3	-14.97
c.3989A>T	Q1330L 2D AIThe SynGAP1 missense variant Q1330L is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, and SIFT. AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields a benign prediction. Foldetta results are unavailable. Overall, the majority of evidence (5 benign vs 3 pathogenic) supports a benign classification. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.943310	Disordered	0.931969	Binding	0.369	0.752	0.875											-3.780	Likely Benign	0.417	Ambiguous	Likely Benign										0.110	Likely Benign	-2.74	Deleterious	0.784	Possibly Damaging	0.341	Benign	3.92	Benign	0.02	Affected			0.0741	0.5480		-2	-2	7.3	-14.97
c.440A>T	Q147L 2D AIThe SynGAP1 missense variant Q147L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, SIFT, ESM1b, and AlphaMissense‑Default; the SGM‑Consensus score is “Likely Pathogenic.” High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic. Foldetta results are unavailable. Overall, the majority of evidence points toward a pathogenic interpretation, and this is not contradicted by any ClinVar classification because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.541878	Disordered	0.503877	Binding	0.349	0.840	0.625											-9.879	Likely Pathogenic	0.740	Likely Pathogenic	Likely Benign										0.185	Likely Benign	-3.51	Deleterious	0.079	Benign	0.037	Benign	3.92	Benign	0.03	Affected			0.0861	0.4927		-2	-2	7.3	-14.97
c.473A>T	Q158L 2D AIThe SynGAP1 missense variant Q158L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign impact for Q158L, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.480142	Structured	0.527565	Binding	0.286	0.750	0.375											-5.965	Likely Benign	0.229	Likely Benign	Likely Benign										0.141	Likely Benign	-1.11	Neutral	0.652	Possibly Damaging	0.160	Benign	4.14	Benign	0.03	Affected			0.0711	0.4832		-2	-2	7.3	-14.97
c.524A>T	Q175L 2D AIThe SynGAP1 missense variant Q175L is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are ESM1b and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 vs 2), and Foldetta results are unavailable. Overall, seven tools favor benign while two favor pathogenic, with no ClinVar evidence to contradict this. Thus, the variant is most likely benign based on the available predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.653063	Disordered	0.474689	Uncertain	0.367	0.618	0.375											-8.699	Likely Pathogenic	0.579	Likely Pathogenic	Likely Benign										0.188	Likely Benign	-2.46	Neutral	0.118	Benign	0.039	Benign	4.10	Benign	0.14	Tolerated			0.0647	0.5109		-2	-2	7.3	-14.97
c.647A>T	Q216L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q216L is not reported in ClinVar (ClinVar ID: None) and has no entry in gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include FoldX, Rosetta, Foldetta, premPS, and FATHMM, while those that predict a pathogenic effect are SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy methods give mixed results: AlphaMissense‑Optimized is uncertain (treated as unavailable), SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic, and Foldetta predicts benign. Overall, the majority of tools (8 pathogenic vs. 5 benign) and the consensus high‑accuracy prediction lean toward pathogenicity. Therefore, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.206376	Structured	0.396100	Uncertain	0.804	0.274	0.000											-11.303	Likely Pathogenic	0.886	Likely Pathogenic	Ambiguous	-0.17	Likely Benign	0.3	0.28	Likely Benign	0.06	Likely Benign	0.30	Likely Benign	0.797	Likely Pathogenic	-5.58	Deleterious	0.963	Probably Damaging	0.452	Possibly Damaging	5.87	Benign	0.01	Affected			0.1036	0.6410		-2	-2	7.3	-14.97
c.740A>T	Q247L 2D AIThe SynGAP1 missense variant Q247L is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include premPS, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b. The remaining tools—FoldX, Rosetta, Foldetta, and AlphaMissense‑Default—return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of evidence (seven pathogenic versus three benign predictions) points to a pathogenic impact, and this conclusion is not contradicted by ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		PH	0.490133	Structured	0.283012	Uncertain	0.822	0.339	0.250											-10.554	Likely Pathogenic	0.352	Ambiguous	Likely Benign	-0.86	Ambiguous	0.5	-1.14	Ambiguous	-1.00	Ambiguous	0.38	Likely Benign	0.687	Likely Pathogenic	-3.89	Deleterious	0.982	Probably Damaging	0.628	Possibly Damaging	5.70	Benign	0.02	Affected			0.0573	0.4129		-2	-2	7.3	-14.97
c.98A>T	Q33L 2D AIThe SynGAP1 missense variant Q33L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as benign. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the preponderance of evidence indicates that the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.707965	Disordered	0.436712	Uncertain	0.342	0.860	0.375											0.253	Likely Benign	0.174	Likely Benign	Likely Benign										0.075	Likely Benign	-1.24	Neutral	0.084	Benign	0.033	Benign	4.18	Benign	0.00	Affected			0.1127	0.6214		-2	-2	7.3	-14.97
c.1002G>C	K334N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K334N is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, and premPS. Tools that predict a pathogenic effect include PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus score, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is “Likely Pathogenic.” Separately, the high‑accuracy AlphaMissense‑Optimized tool predicts pathogenicity, the SGM‑Consensus also predicts pathogenicity, while the Foldetta stability assessment predicts a benign effect. Overall, the majority of predictions (8 pathogenic vs. 5 benign) and the high‑accuracy consensus suggest that K334N is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.377384	Structured	0.325972	Uncertain	0.544	0.414	0.500											-9.581	Likely Pathogenic	0.982	Likely Pathogenic	Likely Pathogenic	0.15	Likely Benign	0.1	-0.25	Likely Benign	-0.05	Likely Benign	0.18	Likely Benign	0.249	Likely Benign	-4.59	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.77	Pathogenic	0.02	Affected			0.3716	0.0958		1	0	0.4	-14.07
c.1002G>T	K334N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K334N is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, and premPS. Tools that predict a pathogenic effect include PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus score, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is “Likely Pathogenic.” Separately, the high‑accuracy AlphaMissense‑Optimized tool predicts pathogenicity, the SGM‑Consensus also predicts pathogenicity, while the Foldetta stability assessment predicts a benign effect. Overall, the majority of predictions (8 pathogenic vs. 5 benign) and the high‑accuracy consensus suggest that K334N is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.377384	Structured	0.325972	Uncertain	0.544	0.414	0.500											-9.581	Likely Pathogenic	0.982	Likely Pathogenic	Likely Pathogenic	0.15	Likely Benign	0.1	-0.25	Likely Benign	-0.05	Likely Benign	0.18	Likely Benign	0.249	Likely Benign	-4.59	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.77	Pathogenic	0.02	Affected			0.3716	0.0958		1	0	0.4	-14.07
c.1008G>C	K336N 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K336N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show discordant results: benign predictions come from REVEL, FoldX, Rosetta, Foldetta, premPS, and polyPhen‑2 HumVar, whereas pathogenic predictions are reported by PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely pathogenic outcome. High‑accuracy assessments further highlight this split: AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus also predicts likely pathogenic, while Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, predicts benign. No prediction or stability result is missing. Overall, the majority of tools and the high‑accuracy methods lean toward pathogenicity, which is consistent with the lack of ClinVar annotation and gnomAD absence. Thus, the variant is most likely pathogenic, and this prediction does not contradict ClinVar status because ClinVar has no entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.318242	Structured	0.338219	Uncertain	0.396	0.428	0.500											-13.307	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic	0.20	Likely Benign	0.1	-0.02	Likely Benign	0.09	Likely Benign	0.20	Likely Benign	0.186	Likely Benign	-4.09	Deleterious	0.801	Possibly Damaging	0.315	Benign	1.59	Pathogenic	0.01	Affected			0.3710	0.1599		1	0	0.4	-14.07
c.1008G>T	K336N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K336N is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, and polyPhen‑2 HumVar. Tools that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (derived from the unanimous pathogenic vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of evidence points toward a pathogenic impact for K336N, and this conclusion does not contradict any ClinVar annotation, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.318242	Structured	0.338219	Uncertain	0.396	0.428	0.500											-13.307	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic	0.20	Likely Benign	0.1	-0.02	Likely Benign	0.09	Likely Benign	0.20	Likely Benign	0.186	Likely Benign	-4.09	Deleterious	0.801	Possibly Damaging	0.315	Benign	1.59	Pathogenic	0.01	Affected			0.3710	0.1599		1	0	0.4	-14.07
c.1011G>C	K337N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K337N is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that indicate a benign effect include REVEL, FoldX, Rosetta, premPS, and SIFT. Tools that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic). High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of predictions (seven pathogenic vs. five benign) and the high‑accuracy consensus lean toward a pathogenic impact. Thus, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.321458	Structured	0.348540	Uncertain	0.449	0.438	0.500											-13.095	Likely Pathogenic	0.986	Likely Pathogenic	Likely Pathogenic	0.12	Likely Benign	0.1	0.36	Likely Benign	0.24	Likely Benign	-0.02	Likely Benign	0.280	Likely Benign	-4.38	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.87	Pathogenic	0.11	Tolerated			0.2945	0.1315		1	0	0.4	-14.07
c.1011G>T	K337N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K337N is not reported in ClinVar and has no entries in gnomAD. Prediction tools that classify it as benign include REVEL, FoldX, Rosetta, premPS, and SIFT, whereas pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, labels the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. With seven tools supporting pathogenicity versus five supporting benign, the overall prediction leans toward pathogenic. No ClinVar entry contradicts this assessment, and the variant is absent from gnomAD, so the pathogenic prediction is not challenged by population data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.321458	Structured	0.348540	Uncertain	0.449	0.438	0.500											-13.095	Likely Pathogenic	0.986	Likely Pathogenic	Likely Pathogenic	0.12	Likely Benign	0.1	0.36	Likely Benign	0.24	Likely Benign	-0.02	Likely Benign	0.280	Likely Benign	-4.38	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.87	Pathogenic	0.11	Tolerated			0.2945	0.1315		1	0	0.4	-14.07
c.1017G>C	K339N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K339N missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, and premPS. Tools that predict a pathogenic effect include PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus score is “Likely Pathogenic.” High‑accuracy assessments: AlphaMissense‑Optimized predicts pathogenic; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates likely pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts benign. Overall, the majority of evidence points to a pathogenic impact for K339N, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.447574	Structured	0.384153	Uncertain	0.535	0.465	0.250											-11.117	Likely Pathogenic	0.983	Likely Pathogenic	Likely Pathogenic	0.20	Likely Benign	0.0	0.35	Likely Benign	0.28	Likely Benign	0.00	Likely Benign	0.410	Likely Benign	-3.88	Deleterious	0.991	Probably Damaging	0.864	Possibly Damaging	1.91	Pathogenic	0.02	Affected			0.3224	0.1158		1	0	0.4	-14.07
c.1017G>T	K339N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K339N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, and premPS. Tools that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic, while Foldetta (combining FoldX‑MD and Rosetta stability outputs) predicts a benign effect. Overall, the majority of evidence points toward a pathogenic impact for K339N, and this conclusion does not contradict any ClinVar annotation, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.447574	Structured	0.384153	Uncertain	0.535	0.465	0.250											-11.117	Likely Pathogenic	0.983	Likely Pathogenic	Likely Pathogenic	0.20	Likely Benign	0.0	0.35	Likely Benign	0.28	Likely Benign	0.00	Likely Benign	0.410	Likely Benign	-3.88	Deleterious	0.991	Probably Damaging	0.864	Possibly Damaging	1.91	Pathogenic	0.02	Affected			0.3224	0.1158		1	0	0.4	-14.07
c.1176G>C	K392N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K392N missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. Tools that predict a pathogenic effect are PROVEAN, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, predicts benign. Overall, the majority of evidence (9 benign vs 3 pathogenic) supports a benign classification. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.541878	Disordered	0.405672	Uncertain	0.319	0.702	0.750											-4.136	Likely Benign	0.780	Likely Pathogenic	Likely Benign	0.24	Likely Benign	0.1	-0.01	Likely Benign	0.12	Likely Benign	0.20	Likely Benign	0.229	Likely Benign	-2.61	Deleterious	0.276	Benign	0.083	Benign	4.60	Benign	0.02	Affected			0.4586	0.2454		1	0	0.4	-14.07
c.1176G>T	K392N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K392N is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. Tools that predict a pathogenic effect are PROVEAN, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑vs‑2 split and is therefore treated as unavailable. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, predicts a benign effect. Overall, the majority of evidence (nine benign vs. three pathogenic predictions) supports a benign classification. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.541878	Disordered	0.405672	Uncertain	0.319	0.702	0.750											-4.136	Likely Benign	0.780	Likely Pathogenic	Likely Benign	0.24	Likely Benign	0.1	-0.01	Likely Benign	0.12	Likely Benign	0.20	Likely Benign	0.229	Likely Benign	-2.61	Deleterious	0.276	Benign	0.083	Benign	4.60	Benign	0.02	Affected			0.4586	0.2454		1	0	0.4	-14.07
c.1182A>C	K394N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K394N missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, FATHMM, and polyPhen‑2 HumVar. Those that agree on a pathogenic effect are Rosetta, PROVEAN, polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. Predictions that are uncertain or inconclusive are Foldetta, premPS, ESM1b, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, Foldetta as uncertain, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic. Overall, the majority of available predictions lean toward pathogenicity, and this conclusion does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.505461	Disordered	0.399336	Uncertain	0.387	0.634	0.625											-7.408	In-Between	0.861	Likely Pathogenic	Ambiguous	0.08	Likely Benign	0.1	2.02	Destabilizing	1.05	Ambiguous	0.66	Ambiguous	0.299	Likely Benign	-3.17	Deleterious	0.535	Possibly Damaging	0.188	Benign	4.60	Benign	0.01	Affected			0.4353	0.2654		1	0	0.4	-14.07
c.1182A>T	K394N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K394N missense variant has no ClinVar entry and is not reported in gnomAD. Functional prediction tools show a mixed signal: benign calls come from REVEL, FoldX, FATHMM, and polyPhen‑2 HumVar, while pathogenic calls come from Rosetta, PROVEAN, polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. Four tools (Foldetta, premPS, ESM1b, AlphaMissense‑Optimized) return uncertain results. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized remains uncertain; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) resolves as pathogenic; and Foldetta is uncertain. Taken together, the majority of evidence—including the high‑accuracy consensus—points to a pathogenic effect. This conclusion is not contradicted by ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.505461	Disordered	0.399336	Uncertain	0.387	0.634	0.625											-7.408	In-Between	0.861	Likely Pathogenic	Ambiguous	0.08	Likely Benign	0.1	2.02	Destabilizing	1.05	Ambiguous	0.66	Ambiguous	0.299	Likely Benign	-3.17	Deleterious	0.535	Possibly Damaging	0.188	Benign	4.60	Benign	0.01	Affected			0.4353	0.2654		1	0	0.4	-14.07
c.1209A>C	K403N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K403N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, Rosetta, and FATHMM, whereas a majority of tools (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized) predict a pathogenic impact. Predictions from FoldX, Foldetta, and premPS are uncertain or inconclusive and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.275179	Structured	0.424920	Uncertain	0.960	0.372	0.000											-10.913	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	1.87	Ambiguous	0.1	0.41	Likely Benign	1.14	Ambiguous	0.74	Ambiguous	0.201	Likely Benign	-4.51	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.73	Benign	0.05	Affected			0.3374	0.2492		1	0	0.4	-14.07
c.1209A>T	K403N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K403N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, Rosetta, and FATHMM, whereas a majority of tools (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized) predict a pathogenic impact. Predictions from FoldX, Foldetta, and premPS are uncertain or inconclusive and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.275179	Structured	0.424920	Uncertain	0.960	0.372	0.000											-10.913	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	1.87	Ambiguous	0.1	0.41	Likely Benign	1.14	Ambiguous	0.74	Ambiguous	0.201	Likely Benign	-4.51	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.73	Benign	0.05	Affected			0.3374	0.2492		1	0	0.4	-14.07
c.1254A>C	K418N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K418N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM. The majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Stability‑based methods (FoldX, Rosetta, premPS, Foldetta) are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic, and Foldetta as uncertain. Overall, the preponderance of evidence indicates that K418N is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.104810	Structured	0.360134	Uncertain	0.948	0.263	0.000											-13.310	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	0.57	Ambiguous	0.0	0.77	Ambiguous	0.67	Ambiguous	0.56	Ambiguous	0.132	Likely Benign	-4.41	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.42	Benign	0.04	Affected			0.3483	0.0606		1	0	0.4	-14.07
c.1254A>T	K418N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K418N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two consensus groups: benign predictions are provided by REVEL and FATHMM, whereas pathogenic predictions are given by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus score (Likely Pathogenic). Stability‑based methods FoldX, Rosetta, Foldetta, and premPS returned uncertain or inconclusive results and are treated as unavailable. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Pathogenic, and Foldetta’s stability analysis is inconclusive. Overall, the majority of reliable predictors classify K418N as pathogenic, and this conclusion does not contradict the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.104810	Structured	0.360134	Uncertain	0.948	0.263	0.000											-13.310	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	0.57	Ambiguous	0.0	0.77	Ambiguous	0.67	Ambiguous	0.56	Ambiguous	0.132	Likely Benign	-4.41	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.42	Benign	0.04	Affected			0.3483	0.0606		1	0	0.4	-14.07
c.1326A>C	K442N 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K442N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, SIFT, FATHMM, and the folding‑stability method Foldetta (which integrates FoldX‑MD and Rosetta outputs). Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM Consensus as likely pathogenic, and Foldetta as benign. Overall, the majority of predictions lean toward pathogenicity, but the presence of several strong benign predictions and a benign folding‑stability result introduces uncertainty. Based on the current computational evidence, the variant is most likely pathogenic, and this does not contradict any ClinVar annotation because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.170161	Structured	0.255766	Uncertain	0.912	0.225	0.000											-11.039	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic	0.37	Likely Benign	0.1	0.53	Ambiguous	0.45	Likely Benign	0.31	Likely Benign	0.161	Likely Benign	-4.05	Deleterious	1.000	Probably Damaging	0.993	Probably Damaging	3.46	Benign	0.10	Tolerated			0.2686	0.1314		1	0	0.4	-14.07
c.1326A>T	K442N 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K442N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, SIFT, FATHMM, and the folding‑stability method Foldetta (which integrates FoldX‑MD and Rosetta outputs). Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM Consensus as likely pathogenic, and Foldetta as benign. Overall, the majority of predictions lean toward pathogenicity, but the presence of several strong benign predictions and a benign folding‑stability result introduces uncertainty. Based on the current computational evidence, the variant is most likely pathogenic, and this does not contradict any ClinVar annotation because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.170161	Structured	0.255766	Uncertain	0.912	0.225	0.000											-11.039	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic	0.37	Likely Benign	0.1	0.53	Ambiguous	0.45	Likely Benign	0.31	Likely Benign	0.161	Likely Benign	-4.05	Deleterious	1.000	Probably Damaging	0.993	Probably Damaging	3.46	Benign	0.10	Tolerated			0.2686	0.1314		1	0	0.4	-14.07
c.1332G>C	K444N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K444N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect are REVEL and FATHMM, whereas the majority of tools (FoldX, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) predict a pathogenic impact. The high‑accuracy methods give the following results: AlphaMissense‑Optimized predicts pathogenic; the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates likely pathogenic; Foldetta’s stability assessment is uncertain and therefore not used as evidence. Overall, the preponderance of evidence points to a pathogenic effect for K444N. This conclusion is not contradicted by ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.203355	Structured	0.262172	Uncertain	0.955	0.213	0.000											-14.797	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	2.41	Destabilizing	0.0	1.52	Ambiguous	1.97	Ambiguous	1.18	Destabilizing	0.286	Likely Benign	-4.77	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.39	Benign	0.01	Affected			0.3282	0.1213		1	0	0.4	-14.07
c.1332G>T	K444N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K444N is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect are REVEL and FATHMM. Tools that predict a pathogenic effect include FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain predictions come from Rosetta and Foldetta. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta as uncertain. Overall, the majority of evidence points to a pathogenic impact. There is no ClinVar annotation to contradict this assessment, so the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.203355	Structured	0.262172	Uncertain	0.955	0.213	0.000											-14.797	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	2.41	Destabilizing	0.0	1.52	Ambiguous	1.97	Ambiguous	1.18	Destabilizing	0.286	Likely Benign	-4.77	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.39	Benign	0.01	Affected			0.3282	0.1213		1	0	0.4	-14.07
c.1380G>C	K460N 2D AIThe SynGAP1 missense variant K460N is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that classify the variant as benign include REVEL, FoldX, Rosetta, SIFT, and FATHMM, whereas those that predict pathogenicity are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support a pathogenic signal: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports the variant as Likely Pathogenic; and the protein‑folding stability method Foldetta, which integrates FoldX‑MD and Rosetta outputs, indicates a benign effect. Overall, the balance of evidence—six pathogenic versus five benign predictions, a pathogenic SGM Consensus, and a pathogenic AlphaMissense‑Optimized—suggests that K460N is most likely pathogenic. This conclusion does not contradict ClinVar status, as the variant is not currently catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.155435	Structured	0.289547	Uncertain	0.938	0.150	0.125											-11.988	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic	0.25	Likely Benign	0.5	0.45	Likely Benign	0.35	Likely Benign	0.89	Ambiguous	0.202	Likely Benign	-4.13	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.29	Benign	0.06	Tolerated			0.3669	0.1599		1	0	0.4	-14.07
c.1380G>T	K460N 2D AIThe SynGAP1 K460N missense variant is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, SIFT, and FATHMM. Tools that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy consensus methods further support a pathogenic interpretation: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is also pathogenic; whereas Foldetta, which integrates FoldX‑MD and Rosetta outputs, indicates a benign effect. Overall, the majority of evidence—including the high‑accuracy tools—points to a pathogenic impact for K460N. This conclusion is not contradicted by ClinVar status, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.155435	Structured	0.289547	Uncertain	0.938	0.150	0.125											-11.988	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic	0.25	Likely Benign	0.5	0.45	Likely Benign	0.35	Likely Benign	0.89	Ambiguous	0.202	Likely Benign	-4.13	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.29	Benign	0.06	Tolerated			0.3669	0.1599		1	0	0.4	-14.07
c.1386G>C	K462N 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K462N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign predictions come from REVEL, SIFT, and FATHMM, whereas pathogenic predictions are returned by PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts Pathogenic, and the SGM Consensus also indicates Likely Pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta outputs, yields an uncertain result, providing no definitive evidence. Overall, the majority of high‑confidence predictors lean toward pathogenicity, contradicting the absence of a ClinVar classification. Thus, the variant is most likely pathogenic based on current predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.264545	Structured	0.297737	Uncertain	0.921	0.159	0.125											-12.823	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	0.69	Ambiguous	0.1	1.67	Ambiguous	1.18	Ambiguous	0.90	Ambiguous	0.304	Likely Benign	-4.83	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.42	Benign	0.07	Tolerated	3.37	34	0.3967	0.1242		0	1	0.4	-14.07
c.1386G>T	K462N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K462N is reported in gnomAD (ID 6‑33438291‑G‑T) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions from REVEL, SIFT, and FATHMM; pathogenic predictions from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Stability‑based methods (FoldX, Rosetta, premPS) and Foldetta are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM Consensus as likely pathogenic, while Foldetta remains uncertain. Overall, the preponderance of evidence points to a pathogenic effect for K462N. This conclusion is not contradicted by ClinVar, which contains no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.264545	Structured	0.297737	Uncertain	0.921	0.159	0.125								6-33438291-G-T	1	6.20e-7	-12.823	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	0.69	Ambiguous	0.1	1.67	Ambiguous	1.18	Ambiguous	0.90	Ambiguous	0.303	Likely Benign	-4.83	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.42	Benign	0.07	Tolerated	3.37	34	0.3967	0.1242		0	1	0.4	-14.07
c.1476A>C	K492N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K492N missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only FATHMM, whereas the remaining tools (REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) uniformly predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. No folding‑stability predictions are definitive. Based on the preponderance of pathogenic predictions and the lack of benign evidence, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.061840	Structured	0.327121	Uncertain	0.947	0.192	0.000											-14.048	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.92	Ambiguous	0.1	1.09	Ambiguous	1.01	Ambiguous	1.25	Destabilizing	0.512	Likely Pathogenic	-4.97	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	2.92	Benign	0.00	Affected			0.2814	0.0926		1	0	0.4	-14.07
c.1476A>T	K492N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K492N missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only FATHMM, whereas the remaining tools (REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) uniformly predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. No folding‑stability predictions are definitive. Based on the preponderance of pathogenic predictions and the lack of benign evidence, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.061840	Structured	0.327121	Uncertain	0.947	0.192	0.000											-14.048	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.92	Ambiguous	0.1	1.09	Ambiguous	1.01	Ambiguous	1.25	Destabilizing	0.512	Likely Pathogenic	-4.97	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	2.92	Benign	0.00	Affected			0.2814	0.0926		1	0	0.4	-14.07
c.1512A>C	K504N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K504N is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, SIFT, and AlphaMissense‑Optimized. Those that predict a pathogenic effect comprise SGM‑Consensus, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default; Rosetta is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of tools (8/13) predict pathogenicity, while 4 predict benign and one is uncertain. Thus, the variant is most likely pathogenic based on the prevailing predictions, and this assessment does not contradict ClinVar status, which is currently absent. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.028107	Structured	0.304984	Uncertain	0.850	0.189	0.000											-8.908	Likely Pathogenic	0.720	Likely Pathogenic	Likely Benign	0.26	Likely Benign	0.2	0.57	Ambiguous	0.42	Likely Benign	1.00	Destabilizing	0.430	Likely Benign	-4.37	Deleterious	0.993	Probably Damaging	0.922	Probably Damaging	-1.44	Pathogenic	0.07	Tolerated			0.2470	0.0926		1	0	0.4	-14.07
c.1512A>T	K504N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K504N missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, SIFT, AlphaMissense‑Optimized, and the folding‑stability method Foldetta. Tools that predict a pathogenic effect comprise SGM‑Consensus, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) labeling it likely pathogenic, and Foldetta indicating a benign folding‑stability outcome. Overall, the majority of predictions (8 out of 13) support a pathogenic interpretation. Thus, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.028107	Structured	0.304984	Uncertain	0.850	0.189	0.000											-8.908	Likely Pathogenic	0.720	Likely Pathogenic	Likely Benign	0.26	Likely Benign	0.2	0.57	Ambiguous	0.42	Likely Benign	1.00	Destabilizing	0.430	Likely Benign	-4.37	Deleterious	0.993	Probably Damaging	0.922	Probably Damaging	-1.44	Pathogenic	0.07	Tolerated			0.2470	0.0926		1	0	0.4	-14.07
c.1521G>C	K507N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K507N is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include Rosetta, PROVEAN, SIFT, and AlphaMissense‑Optimized, whereas a pathogenic signal is reported by REVEL, premPS, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default; FoldX and Foldetta give uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts pathogenic. Foldetta’s stability prediction is unavailable. Overall, the majority of tools (10 out of 14 with definitive calls) predict a pathogenic impact, and this conclusion does not contradict any ClinVar annotation because no ClinVar status exists. Thus, the variant is most likely pathogenic based on the available computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.019401	Structured	0.262601	Uncertain	0.885	0.222	0.000											-10.682	Likely Pathogenic	0.739	Likely Pathogenic	Likely Benign	0.81	Ambiguous	0.1	0.18	Likely Benign	0.50	Ambiguous	1.06	Destabilizing	0.579	Likely Pathogenic	-1.63	Neutral	1.000	Probably Damaging	0.999	Probably Damaging	-1.57	Pathogenic	0.11	Tolerated			0.2417	0.0764		1	0	0.4	-14.07
c.1521G>T	K507N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K507N is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include Rosetta, PROVEAN, SIFT, and AlphaMissense‑Optimized, while those that predict a pathogenic effect comprise REVEL, premPS, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default; FoldX and Foldetta are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of tools (10 pathogenic vs. 4 benign) predict a deleterious impact. Thus, the variant is most likely pathogenic, and this prediction does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.019401	Structured	0.262601	Uncertain	0.885	0.222	0.000											-10.682	Likely Pathogenic	0.739	Likely Pathogenic	Likely Benign	0.81	Ambiguous	0.1	0.18	Likely Benign	0.50	Ambiguous	1.06	Destabilizing	0.579	Likely Pathogenic	-1.63	Neutral	1.000	Probably Damaging	0.999	Probably Damaging	-1.57	Pathogenic	0.11	Tolerated			0.2417	0.0764		1	0	0.4	-14.07
c.1590G>C	K530N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K530N missense variant is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that indicate a benign effect include FoldX, Rosetta, and Foldetta, whereas the remaining tools—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus—predict a pathogenic or likely pathogenic outcome; premPS is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta as benign. Overall, the majority of predictions (10/13) support pathogenicity, with only three tools indicating benign. Therefore, the variant is most likely pathogenic based on the available computational evidence, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.308712	Structured	0.018455	Uncertain	0.891	0.409	0.000											-12.459	Likely Pathogenic	0.960	Likely Pathogenic	Likely Pathogenic	0.42	Likely Benign	0.1	0.23	Likely Benign	0.33	Likely Benign	0.56	Ambiguous	0.553	Likely Pathogenic	-4.18	Deleterious	0.950	Possibly Damaging	0.703	Possibly Damaging	-1.65	Pathogenic	0.00	Affected			0.2350	0.1086		1	0	0.4	-14.07
c.1590G>T	K530N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K530N missense variant is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that indicate a benign effect include FoldX, Rosetta, and Foldetta, whereas the remaining tools—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus—predict a pathogenic or likely pathogenic outcome; premPS is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta as benign. Overall, the majority of predictions (10/13) support pathogenicity, with only three tools indicating benign. Therefore, the variant is most likely pathogenic based on the available computational evidence, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.308712	Structured	0.018455	Uncertain	0.891	0.409	0.000											-12.459	Likely Pathogenic	0.960	Likely Pathogenic	Likely Pathogenic	0.42	Likely Benign	0.1	0.23	Likely Benign	0.33	Likely Benign	0.56	Ambiguous	0.553	Likely Pathogenic	-4.18	Deleterious	0.950	Possibly Damaging	0.703	Possibly Damaging	-1.65	Pathogenic	0.00	Affected			0.2350	0.1086		1	0	0.4	-14.07
c.1659G>C	K553N 2D 3DClick to see structure in 3D Viewer AISynGAP1 K553N is not reported in ClinVar and is present in gnomAD (6-33438902-G-C). Functional prediction tools largely agree on a deleterious effect: SIFT is the sole benign predictor, whereas REVEL, SGM‑Consensus, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity. FoldX, Rosetta, and Foldetta return uncertain results. High‑accuracy assessments reinforce the pathogenic signal: AlphaMissense‑Optimized is pathogenic, SGM‑Consensus is likely pathogenic, and Foldetta remains uncertain. Overall, the consensus of the majority of tools indicates that K553N is most likely pathogenic, and this conclusion is consistent with the absence of a ClinVar entry (no contradiction). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.012270	Structured	0.006539	Uncertain	0.949	0.246	0.000								6-33438902-G-C	1	6.20e-7	-13.664	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.63	Ambiguous	0.0	0.62	Ambiguous	0.63	Ambiguous	1.11	Destabilizing	0.566	Likely Pathogenic	-4.77	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.24	Pathogenic	0.11	Tolerated	3.37	35	0.2758	0.0926		0	1	0.4	-14.07
c.1659G>T	K553N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K553N missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only SIFT, whereas the majority of algorithms (SGM‑Consensus, REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic impact; FoldX, Rosetta, and Foldetta are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic, and Foldetta as uncertain. Taken together, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.012270	Structured	0.006539	Uncertain	0.949	0.246	0.000											-13.664	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.63	Ambiguous	0.0	0.62	Ambiguous	0.63	Ambiguous	1.11	Destabilizing	0.566	Likely Pathogenic	-4.77	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.24	Pathogenic	0.11	Tolerated	3.37	35	0.2758	0.0926		0	1	0.4	-14.07
c.1698G>C	K566N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K566N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that assess pathogenicity uniformly indicate a deleterious effect: REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity, while Rosetta is uncertain. No tool predicts a benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Consequently, the variant is most likely pathogenic based on the available predictions, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.027463	Structured	0.047887	Uncertain	0.924	0.219	0.000											-11.255	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	2.83	Destabilizing	0.3	1.33	Ambiguous	2.08	Destabilizing	1.32	Destabilizing	0.683	Likely Pathogenic	-4.04	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.43	Pathogenic	0.03	Affected	3.37	35	0.3042	0.1567		0	1	0.4	-14.07
c.1698G>T	K566N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K566N is listed in gnomAD (variant ID 6‑33440750‑G‑T) but has no ClinVar entry. All available in‑silico predictors that provide a definitive call classify the substitution as pathogenic: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The only tool with an inconclusive result is Rosetta (Uncertain), which is treated as unavailable evidence. High‑accuracy methods reinforce this assessment: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. Consequently, the variant is most likely pathogenic based on current predictions, and this conclusion does not contradict any ClinVar status because none is reported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.027463	Structured	0.047887	Uncertain	0.924	0.219	0.000								6-33440750-G-T			-11.255	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	2.83	Destabilizing	0.3	1.33	Ambiguous	2.08	Destabilizing	1.32	Destabilizing	0.683	Likely Pathogenic	-4.04	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.43	Pathogenic	0.03	Affected	3.37	35	0.3042	0.1567		0	1	0.4	-14.07
c.1884G>C	K628N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K628N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated algorithms—premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—classify the variant as pathogenic or likely pathogenic. FoldX, Rosetta, and Foldetta provide uncertain or inconclusive stability predictions and are therefore treated as unavailable evidence. High‑accuracy assessments specifically show AlphaMissense‑Optimized predicting pathogenicity, the SGM‑Consensus indicating a likely pathogenic status, and Foldetta yielding an uncertain result. Based on the overwhelming agreement among the majority of prediction tools, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.088832	Structured	0.035486	Uncertain	0.957	0.229	0.000											-12.284	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	0.78	Ambiguous	0.1	0.59	Ambiguous	0.69	Ambiguous	1.11	Destabilizing	0.403	Likely Benign	-4.98	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	2.37	Pathogenic	0.00	Affected	3.37	34	0.2740	0.1254		0	1	0.4	-14.07
c.1884G>T	K628N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K628N is catalogued in gnomAD (6‑33440936‑G‑T) but has no ClinVar entry. Functional prediction tools cluster into two groups: a single benign prediction from REVEL, and a consensus of nine pathogenic predictions from premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also labels the variant as Likely Pathogenic. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus confirms a likely pathogenic status, and Foldetta, which integrates FoldX‑MD and Rosetta outputs, yields an uncertain result and therefore does not alter the overall interpretation. Consequently, the variant is most likely pathogenic according to the available computational evidence, and this assessment is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.088832	Structured	0.035486	Uncertain	0.957	0.229	0.000								6-33440936-G-T	1	6.20e-7	-12.284	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	0.78	Ambiguous	0.1	0.59	Ambiguous	0.69	Ambiguous	1.11	Destabilizing	0.403	Likely Benign	-4.98	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	2.37	Pathogenic	0.00	Affected	3.37	34	0.2740	0.1254		0	1	0.4	-14.07
c.1914G>C	K638N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K638N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, premPS, and FATHMM, whereas a majority of tools (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default) predict a pathogenic impact. Predictions that are inconclusive or unavailable are FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN), and Foldetta as uncertain. Overall, the balance of evidence favors a pathogenic classification; this conclusion does not contradict ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.045352	Structured	0.098064	Uncertain	0.937	0.260	0.000											-9.420	Likely Pathogenic	0.947	Likely Pathogenic	Ambiguous	0.74	Ambiguous	0.1	0.90	Ambiguous	0.82	Ambiguous	0.40	Likely Benign	0.256	Likely Benign	-4.59	Deleterious	1.000	Probably Damaging	0.989	Probably Damaging	3.40	Benign	0.02	Affected			0.2875	0.1126		1	0	0.4	-14.07
c.1914G>T	K638N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K638N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, premPS, and FATHMM, whereas a majority of tools (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default) predict a pathogenic impact. Predictions that are inconclusive or unavailable are FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN), and Foldetta as uncertain. Overall, the balance of evidence favors a pathogenic classification; this conclusion does not contradict ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.045352	Structured	0.098064	Uncertain	0.937	0.260	0.000											-9.420	Likely Pathogenic	0.947	Likely Pathogenic	Ambiguous	0.74	Ambiguous	0.1	0.90	Ambiguous	0.82	Ambiguous	0.40	Likely Benign	0.256	Likely Benign	-4.59	Deleterious	1.000	Probably Damaging	0.989	Probably Damaging	3.40	Benign	0.02	Affected			0.2875	0.1126		1	0	0.4	-14.07
c.1926G>C	K642N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K642N missense variant is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, FATHMM, and polyPhen‑2 HumVar. Tools that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy methods give a pathogenic signal: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, while Foldetta (combining FoldX‑MD and Rosetta outputs) is benign. With two of the three high‑accuracy tools supporting pathogenicity and an overall balance of predictions, the variant is most likely pathogenic. This assessment does not contradict ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.061840	Structured	0.181468	Uncertain	0.806	0.289	0.000											-11.423	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	0.25	Likely Benign	0.0	0.05	Likely Benign	0.15	Likely Benign	0.48	Likely Benign	0.273	Likely Benign	-4.88	Deleterious	0.958	Probably Damaging	0.392	Benign	2.88	Benign	0.00	Affected			0.3553	0.1590		1	0	0.4	-14.07
c.1926G>T	K642N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K642N is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, and FATHMM, while those that predict a pathogenic impact are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and polyPhen‑2 HumVar (benign). High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta as benign. Overall, seven tools favor pathogenicity versus six favoring benign, and the high‑accuracy predictions are mixed. Thus, the variant is most likely pathogenic based on the preponderance of evidence, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.061840	Structured	0.181468	Uncertain	0.806	0.289	0.000											-11.423	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	0.25	Likely Benign	0.0	0.05	Likely Benign	0.15	Likely Benign	0.48	Likely Benign	0.274	Likely Benign	-4.88	Deleterious	0.958	Probably Damaging	0.392	Benign	2.88	Benign	0.00	Affected			0.3553	0.1590		1	0	0.4	-14.07
c.2115G>C	K705N 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K705N is listed in ClinVar (ID 872011.0) as Pathogenic and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions (REVEL, Rosetta, premPS, FATHMM) and pathogenic predictions (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default). Uncertain results come from FoldX, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is inconclusive, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—classifies the variant as Likely Pathogenic, and Foldetta also yields an uncertain stability change. Overall, the preponderance of evidence indicates the variant is most likely pathogenic, which aligns with its ClinVar classification and does not contradict the reported status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.134866	Structured	0.379324	Uncertain	0.922	0.364	0.000					Likely Pathogenic		1				-9.767	Likely Pathogenic	0.925	Likely Pathogenic	Ambiguous	0.74	Ambiguous	0.0	0.37	Likely Benign	0.56	Ambiguous	0.44	Likely Benign	0.183	Likely Benign	-3.12	Deleterious	0.996	Probably Damaging	0.876	Possibly Damaging	3.37	Benign	0.02	Affected	3.47	10	0.2480	0.1124		1	0	0.4	-14.07	221.4	-20.2	0.0	0.0	0.0	0.1						X		Uncertain	The amino side chain of Lys705, located at the end and outer surface of an α-helix (res. Thr704-Gly712), does not form any interactions in the WT simulations. In the variant simulations, the carboxamide side chain of Asn705 briefly forms a salt bridge with Glu706. However, there is no apparent difference between the systems. Due to the model ending abruptly at the C-terminus, no definite conclusions can be drawn based on the simulations.
c.2115G>T	K705N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K705N is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL, Rosetta, premPS, and FATHMM, while pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Three tools (FoldX, Foldetta, AlphaMissense‑Optimized) give uncertain or inconclusive results. High‑accuracy assessments further support a pathogenic interpretation: the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is “Likely Pathogenic”; AlphaMissense‑Optimized remains uncertain, and Foldetta is also uncertain. Overall, the balance of evidence favors a pathogenic effect for K705N, and this conclusion does not contradict the current ClinVar status, which has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.134866	Structured	0.379324	Uncertain	0.922	0.364	0.000											-9.767	Likely Pathogenic	0.925	Likely Pathogenic	Ambiguous	0.74	Ambiguous	0.0	0.37	Likely Benign	0.56	Ambiguous	0.44	Likely Benign	0.183	Likely Benign	-3.12	Deleterious	0.996	Probably Damaging	0.876	Possibly Damaging	3.37	Benign	0.02	Affected	3.47	10	0.2480	0.1124		1	0	0.4	-14.07	221.4	-20.2	0.0	0.0	0.0	0.1						X		Uncertain	The amino side chain of Lys705, located at the end and outer surface of an α-helix (res. Thr704-Gly712), does not form any interactions in the WT simulations. In the variant simulations, the carboxamide side chain of Asn705 briefly forms a salt bridge with Glu706. However, there is no apparent difference between the systems. Due to the model ending abruptly at the C-terminus, no definite conclusions can be drawn based on the simulations.
c.2130G>C	K710N 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K710N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL, premPS, and FATHMM, while pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). Uncertain or unavailable results are reported for FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is inconclusive, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Pathogenic, and Foldetta remains uncertain. Overall, the preponderance of evidence points to a pathogenic impact for K710N, and this conclusion does not conflict with the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.321458	Structured	0.370438	Uncertain	0.949	0.368	0.000											-9.330	Likely Pathogenic	0.943	Likely Pathogenic	Ambiguous	0.85	Ambiguous	0.0	0.50	Ambiguous	0.68	Ambiguous	0.33	Likely Benign	0.201	Likely Benign	-4.39	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.42	Benign	0.04	Affected			0.2485	0.1124		1	0	0.4	-14.07
c.2130G>T	K710N 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K710N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that indicate a benign effect include REVEL, premPS, and FATHMM. In contrast, a majority of algorithms predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy assessment shows AlphaMissense‑Optimized as uncertain, SGM‑Consensus (derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the balance of evidence favors a pathogenic interpretation, and this conclusion does not conflict with the ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.321458	Structured	0.370438	Uncertain	0.949	0.368	0.000											-9.330	Likely Pathogenic	0.943	Likely Pathogenic	Ambiguous	0.85	Ambiguous	0.0	0.50	Ambiguous	0.68	Ambiguous	0.33	Likely Benign	0.201	Likely Benign	-4.39	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.42	Benign	0.04	Affected			0.2485	0.1124		1	0	0.4	-14.07
c.2373G>C	K791N 2D AIThe SynGAP1 missense variant K791N is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain, and Foldetta (combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Overall, the majority of high‑accuracy predictions (SGM‑Consensus, AlphaMissense‑Optimized uncertain, Foldetta unavailable) lean toward a benign interpretation, with only two pathogenic calls. Thus, based on the current computational evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.966441	Disordered	0.478670	Uncertain	0.356	0.896	0.875											-4.001	Likely Benign	0.794	Likely Pathogenic	Ambiguous										0.027	Likely Benign	-1.26	Neutral	0.666	Possibly Damaging	0.267	Benign	4.14	Benign	0.13	Tolerated			0.4578	0.1354		1	0	0.4	-14.07
c.2373G>T	K791N 2D AIThe SynGAP1 missense variant K791N is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Overall, the majority of high‑accuracy predictions (including the SGM‑Consensus) indicate a benign impact, and there is no conflict with ClinVar status. Thus, based on the current computational evidence, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.966441	Disordered	0.478670	Uncertain	0.356	0.896	0.875											-4.001	Likely Benign	0.794	Likely Pathogenic	Ambiguous										0.027	Likely Benign	-1.26	Neutral	0.666	Possibly Damaging	0.267	Benign	4.14	Benign	0.13	Tolerated			0.4578	0.1354		1	0	0.4	-14.07
c.2379G>C	K793N 2D AIThe SynGAP1 missense variant K793N is catalogued in gnomAD (6‑33442931‑G‑C) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM all classify it as benign, and the SGM‑Consensus score (Likely Benign) supports this view. Only AlphaMissense‑Default predicts pathogenicity. High‑accuracy assessments further reinforce the benign prediction: AlphaMissense‑Optimized reports a benign outcome, and the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—also yields a benign classification. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence indicates that K793N is most likely benign, and this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.971072	Disordered	0.426071	Uncertain	0.344	0.901	0.875								6-33442931-G-C	4	2.48e-6	-5.162	Likely Benign	0.632	Likely Pathogenic	Likely Benign										0.040	Likely Benign	1.18	Neutral	0.174	Benign	0.135	Benign	4.13	Benign	0.47	Tolerated	4.07	3	0.4429	0.1976		0	1	0.4	-14.07
c.2379G>T	K793N 2D AIThe SynGAP1 missense variant K793N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all classify the change as benign. Only AlphaMissense‑Default predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” consensus. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority vote) is also benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none exists). Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.971072	Disordered	0.426071	Uncertain	0.344	0.901	0.875											-5.162	Likely Benign	0.632	Likely Pathogenic	Likely Benign										0.040	Likely Benign	1.18	Neutral	0.174	Benign	0.135	Benign	4.13	Benign	0.47	Tolerated	4.07	3	0.4429	0.1976		0	1	0.4	-14.07
c.2409A>C	K803N 2D AIThe SynGAP1 K803N missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and ESM1b, whereas those that agree on a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized tool rates the variant as uncertain, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive because it yields a 2‑to‑2 split. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, more tools predict pathogenicity (five) than benignity (three), and the high‑accuracy assessments do not overturn this trend. Therefore, the variant is most likely pathogenic based on current predictions, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.827927	Disordered	0.733908	Binding	0.349	0.900	0.625											-5.039	Likely Benign	0.807	Likely Pathogenic	Ambiguous										0.045	Likely Benign	-2.13	Neutral	0.896	Possibly Damaging	0.673	Possibly Damaging	2.34	Pathogenic	0.00	Affected			0.3805	0.2035		1	0	0.4	-14.07
c.2409A>T	K803N 2D AIThe SynGAP1 K803N missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and ESM1b, whereas those that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized tool returns an uncertain result, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive because it yields a 2‑to‑2 split. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, more tools (five) predict pathogenicity than benign (three), and the high‑accuracy assessments do not overturn this trend. Therefore, the variant is most likely pathogenic based on current predictions, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.827927	Disordered	0.733908	Binding	0.349	0.900	0.625											-5.039	Likely Benign	0.807	Likely Pathogenic	Ambiguous										0.045	Likely Benign	-2.13	Neutral	0.896	Possibly Damaging	0.673	Possibly Damaging	2.34	Pathogenic	0.00	Affected			0.3805	0.2035		1	0	0.4	-14.07
c.240A>C	K80N 2D AIThe SynGAP1 K80N missense variant has no ClinVar record and is not reported in gnomAD. Functional prediction tools that agree on benign impact include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, and FATHMM, while those that predict pathogenicity are polyPhen‑2 HumDiv, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized predicting pathogenicity, whereas the SGM‑Consensus (majority vote) predicts benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the overall distribution of predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.637480	Disordered	0.477530	Uncertain	0.331	0.873	0.500											-5.072	Likely Benign	0.958	Likely Pathogenic	Likely Pathogenic										0.078	Likely Benign	-1.07	Neutral	0.588	Possibly Damaging	0.054	Benign	3.89	Benign	0.00	Affected			0.3749	0.1237		1	0	0.4	-14.07
c.240A>T	K80N 2D AIThe SynGAP1 K80N missense variant has no ClinVar record and is not listed in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as “Likely Benign.” High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus (majority vote) remains benign; Foldetta results are unavailable. Based on the overall distribution of predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.637480	Disordered	0.477530	Uncertain	0.331	0.873	0.500											-5.072	Likely Benign	0.958	Likely Pathogenic	Likely Pathogenic										0.078	Likely Benign	-1.07	Neutral	0.588	Possibly Damaging	0.054	Benign	3.89	Benign	0.00	Affected			0.3749	0.1237		1	0	0.4	-14.07
c.2499G>C	K833N 2D AIThe SynGAP1 missense variant K833N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also as benign; Foldetta results are unavailable. Overall, the balance of evidence favors a benign interpretation. This conclusion is consistent with the lack of a ClinVar assertion, so there is no contradiction with existing clinical database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.671169	Disordered	0.625797	Binding	0.315	0.863	0.375											-2.759	Likely Benign	0.579	Likely Pathogenic	Likely Benign										0.087	Likely Benign	-1.02	Neutral	0.999	Probably Damaging	0.966	Probably Damaging	2.61	Benign	0.02	Affected			0.3088	0.1464		1	0	0.4	-14.07
c.2499G>T	K833N 2D AIThe SynGAP1 missense variant K833N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for K833N, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.671169	Disordered	0.625797	Binding	0.315	0.863	0.375											-2.759	Likely Benign	0.579	Likely Pathogenic	Likely Benign										0.087	Likely Benign	-1.02	Neutral	0.999	Probably Damaging	0.966	Probably Damaging	2.61	Benign	0.02	Affected			0.3088	0.1464		1	0	0.4	-14.07
c.2517G>C	K839N 2D AIThe SynGAP1 missense variant K839N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated predictors—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus also indicates Likely Pathogenic. Foldetta results are unavailable. Overall, the preponderance of evidence from multiple in silico tools indicates that K839N is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.642678	Disordered	0.611185	Binding	0.282	0.865	0.375											-10.939	Likely Pathogenic	0.962	Likely Pathogenic	Likely Pathogenic										0.093	Likely Benign	-2.94	Deleterious	0.996	Probably Damaging	0.951	Probably Damaging	2.44	Pathogenic	0.01	Affected			0.3629	0.1876		1	0	0.4	-14.07
c.2517G>T	K839N 2D AIThe SynGAP1 missense variant K839N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized returns a pathogenic score, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Pathogenic. Foldetta results are unavailable. Overall, the preponderance of evidence indicates that K839N is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.642678	Disordered	0.611185	Binding	0.282	0.865	0.375											-10.939	Likely Pathogenic	0.962	Likely Pathogenic	Likely Pathogenic										0.093	Likely Benign	-2.94	Deleterious	0.996	Probably Damaging	0.951	Probably Damaging	2.44	Pathogenic	0.01	Affected			0.3629	0.1876		1	0	0.4	-14.07
c.2952G>C	K984N 2D AIThe SynGAP1 missense variant K984N is catalogued in gnomAD (6‑33443504‑G‑C) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, ESM1b, and FATHMM, while pathogenic predictions arise from polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. High‑accuracy assessments are mixed: AlphaMissense‑Optimized rates the variant as uncertain, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) labels it “Likely Benign,” and Foldetta (which integrates FoldX‑MD and Rosetta outputs) has no available result for this residue. Overall, the balance of evidence leans toward a benign effect, with no pathogenic ClinVar classification to contradict this inference. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.703578	Disordered	0.951648	Binding	0.288	0.895	0.750								6-33443504-G-C	1	6.20e-7	-3.020	Likely Benign	0.955	Likely Pathogenic	Ambiguous										0.091	Likely Benign	0.52	Neutral	0.951	Possibly Damaging	0.637	Possibly Damaging	2.89	Benign	0.00	Affected	4.32	1	0.4138	0.1677		0	1	0.4	-14.07
c.2952G>T	K984N 2D AISynGAP1 missense variant K984N has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict pathogenicity are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments are mixed: AlphaMissense‑Optimized is Uncertain, SGM‑Consensus is Likely Benign, and Foldetta results are unavailable. Overall, the balance of evidence leans toward a benign interpretation, and this assessment does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.703578	Disordered	0.951648	Binding	0.288	0.895	0.750											-3.020	Likely Benign	0.955	Likely Pathogenic	Ambiguous										0.091	Likely Benign	0.52	Neutral	0.951	Possibly Damaging	0.637	Possibly Damaging	2.89	Benign	0.00	Affected	4.32	1	0.4138	0.1677		0	1	0.4	-14.07
c.2982G>C	K994N 2D AIThe SynGAP1 missense variant K994N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized all classify the change as benign, while the only pathogenic call comes from SIFT. AlphaMissense‑Default is uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports the variant as Likely Benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, SGM‑Consensus confirms a Likely Benign status, and Foldetta data are unavailable. Taken together, the preponderance of evidence indicates that K994N is most likely benign, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.862302	Disordered	0.930054	Binding	0.289	0.912	0.750											-3.724	Likely Benign	0.519	Ambiguous	Likely Benign										0.011	Likely Benign	-0.73	Neutral	0.255	Benign	0.113	Benign	4.09	Benign	0.01	Affected			0.4010	0.2376		1	0	0.4	-14.07
c.2982G>T	K994N 2D AIThe SynGAP1 missense variant K994N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized all classify the change as benign, while the only pathogenic call comes from SIFT. AlphaMissense‑Default is uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports the variant as Likely Benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, SGM‑Consensus confirms a Likely Benign status, and Foldetta data are unavailable. Taken together, the preponderance of evidence indicates that K994N is most likely benign, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.862302	Disordered	0.930054	Binding	0.289	0.912	0.750											-3.724	Likely Benign	0.519	Ambiguous	Likely Benign										0.009	Likely Benign	-0.73	Neutral	0.255	Benign	0.113	Benign	4.09	Benign	0.01	Affected			0.4010	0.2376		1	0	0.4	-14.07
c.3216G>C	K1072N 2D AIThe SynGAP1 missense variant K1072N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as “Uncertain” and the SGM‑Consensus as “Likely Benign”; Foldetta results are not available. Overall, the balance of evidence leans toward a benign impact, with no ClinVar entry to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.922952	Disordered	0.984675	Binding	0.307	0.907	0.750											-2.215	Likely Benign	0.953	Likely Pathogenic	Ambiguous										0.078	Likely Benign	-1.18	Neutral	0.999	Probably Damaging	0.995	Probably Damaging	3.92	Benign	0.05	Affected			0.3449	0.2391		1	0	0.4	-14.07
c.3216G>T	K1072N 2D AIThe SynGAP1 missense variant K1072N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as “Uncertain” and the SGM‑Consensus as “Likely Benign”; Foldetta results are not available. Overall, the balance of evidence leans toward a benign impact, with no ClinVar entry to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.922952	Disordered	0.984675	Binding	0.307	0.907	0.750											-2.215	Likely Benign	0.953	Likely Pathogenic	Ambiguous										0.078	Likely Benign	-1.18	Neutral	0.999	Probably Damaging	0.995	Probably Damaging	3.92	Benign	0.05	Affected			0.3449	0.2391		1	0	0.4	-14.07
c.3249A>C	K1083N 2D AIThe SynGAP1 missense variant K1083N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Benign, and Foldetta results are unavailable. Overall, the balance of evidence leans toward a benign interpretation, with no conflict with ClinVar status because no ClinVar assertion exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.837511	Disordered	0.978906	Binding	0.302	0.893	1.000											-4.088	Likely Benign	0.873	Likely Pathogenic	Ambiguous										0.053	Likely Benign	-0.83	Neutral	0.999	Probably Damaging	0.995	Probably Damaging	4.04	Benign	0.21	Tolerated			0.3939	0.2234		1	0	0.4	-14.07
c.3249A>T	K1083N 2D AIThe SynGAP1 missense variant K1083N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Benign, and Foldetta results are unavailable. Overall, the balance of evidence leans toward a benign interpretation, with no conflict with ClinVar status because no ClinVar assertion exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.837511	Disordered	0.978906	Binding	0.302	0.893	1.000											-4.088	Likely Benign	0.873	Likely Pathogenic	Ambiguous										0.053	Likely Benign	-0.83	Neutral	0.999	Probably Damaging	0.995	Probably Damaging	4.04	Benign	0.21	Tolerated			0.3939	0.2234		1	0	0.4	-14.07
c.324G>C	K108N 2D AISynGAP1 missense variant K108N is reported in gnomAD (6‑33432189‑G‑C) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign calls from REVEL, PROVEAN, ESM1b, FATHMM, and the SGM‑Consensus (Likely Benign); pathogenic calls from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized predicting pathogenic, whereas the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely benign; Foldetta results are unavailable. Consequently, the evidence is evenly split, with no single prediction dominating. The variant is therefore not clearly benign or pathogenic based on current computational data, and this lack of consensus does not contradict any ClinVar classification, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.626927	Disordered	0.673331	Binding	0.338	0.858	0.875								6-33432189-G-C	1	6.20e-7	-3.015	Likely Benign	0.964	Likely Pathogenic	Likely Pathogenic										0.068	Likely Benign	-1.35	Neutral	0.998	Probably Damaging	0.981	Probably Damaging	4.07	Benign	0.03	Affected	3.61	5	0.3904	0.1820		0	1	0.4	-14.07
c.324G>T	K108N 2D AIThe SynGAP1 missense variant K108N is not reported in ClinVar and has no gnomAD entry. Consensus predictions from multiple in‑silico tools are split: benign calls come from REVEL, PROVEAN, ESM1b, FATHMM, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) which labels the variant as Likely Benign. Pathogenic calls arise from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized, the latter two high‑accuracy predictors both flagging the variant as Pathogenic. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, did not return a result for this variant, so its stability impact is unavailable. Overall, the majority of high‑confidence tools (AlphaMissense‑Optimized and the SGM‑Consensus) disagree, with AlphaMissense‑Optimized indicating pathogenicity while the consensus suggests benign. Because ClinVar contains no classification, there is no contradiction; the variant is most likely pathogenic based on the most reliable predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.626927	Disordered	0.673331	Binding	0.338	0.858	0.875											-3.015	Likely Benign	0.964	Likely Pathogenic	Likely Pathogenic										0.068	Likely Benign	-1.35	Neutral	0.998	Probably Damaging	0.981	Probably Damaging	4.07	Benign	0.03	Affected	3.61	5	0.3904	0.1820		0	1	0.4	-14.07
c.3333G>C	K1111N 2D AIThe SynGAP1 missense variant K1111N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and AlphaMissense‑Default. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Benign, and AlphaMissense‑Optimized is uncertain. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact. There is no ClinVar entry to contradict this assessment, so the variant is most likely benign based on current predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.910643	Disordered	0.921455	Binding	0.300	0.902	0.875											-4.503	Likely Benign	0.833	Likely Pathogenic	Ambiguous										0.048	Likely Benign	-0.77	Neutral	0.666	Possibly Damaging	0.211	Benign	2.64	Benign	0.15	Tolerated			0.3667	0.2350		1	0	0.4	-14.07
c.3333G>T	K1111N 2D AIThe SynGAP1 missense variant K1111N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and AlphaMissense‑Default. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Benign, and AlphaMissense‑Optimized is uncertain. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.910643	Disordered	0.921455	Binding	0.300	0.902	0.875											-4.503	Likely Benign	0.833	Likely Pathogenic	Ambiguous										0.048	Likely Benign	-0.77	Neutral	0.666	Possibly Damaging	0.211	Benign	2.64	Benign	0.15	Tolerated			0.3667	0.2350		1	0	0.4	-14.07
c.3390G>C	K1130N 2D AIThe SynGAP1 missense variant K1130N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) which classifies it as Likely Benign. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized result is uncertain, and Foldetta (combining FoldX‑MD and Rosetta outputs) has no available prediction for this variant. Overall, the majority of evidence points to a benign impact. The variant’s predicted benign status does not contradict ClinVar, as no ClinVar entry exists. Thus, based on current computational predictions, the K1130N variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.903857	Disordered	0.863782	Binding	0.350	0.904	0.750											-4.822	Likely Benign	0.946	Likely Pathogenic	Ambiguous										0.336	Likely Benign	-1.02	Neutral	0.818	Possibly Damaging	0.287	Benign	5.43	Benign	0.00	Affected			0.4119	0.2393		1	0	0.4	-14.07
c.3390G>T	K1130N 2D AIThe SynGAP1 missense variant K1130N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) which classifies it as Likely Benign. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized result is uncertain, and Foldetta (combining FoldX‑MD and Rosetta outputs) has no available prediction for this variant. Overall, the majority of evidence points to a benign impact. The variant’s predicted benign status does not contradict ClinVar, as no ClinVar entry exists. Thus, based on current computational predictions, the K1130N variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.903857	Disordered	0.863782	Binding	0.350	0.904	0.750											-4.822	Likely Benign	0.946	Likely Pathogenic	Ambiguous										0.336	Likely Benign	-1.02	Neutral	0.818	Possibly Damaging	0.287	Benign	5.43	Benign	0.00	Affected			0.4119	0.2393		1	0	0.4	-14.07
c.3405G>C	K1135N 2D AIThe SynGAP1 missense variant K1135N is listed in ClinVar (ID 633521.0) with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM. In contrast, AlphaMissense‑Default and AlphaMissense‑Optimized both predict a pathogenic outcome. High‑accuracy assessments further show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) remains Likely Benign. No Foldetta (FoldX‑MD/Rosetta stability) result is available for this variant. Overall, the majority of predictions support a benign classification, which does not contradict the current ClinVar “Uncertain” designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.887230	Disordered	0.790969	Binding	0.303	0.889	0.875					Uncertain		1				-5.715	Likely Benign	0.960	Likely Pathogenic	Likely Pathogenic										0.166	Likely Benign	-0.97	Neutral	0.411	Benign	0.321	Benign	5.43	Benign	0.07	Tolerated	4.32	2	0.4152	0.1793		1	0	0.4	-14.07
c.3405G>T	K1135N 2D AIThe SynGAP1 missense variant K1135N is not reported in ClinVar (ClinVar ID None) but is present in gnomAD (ID 6‑33443957‑G‑T). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and FATHMM. Tools that predict a pathogenic effect are AlphaMissense‑Default and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus remains likely benign; Foldetta results are unavailable. Overall, the majority of predictions (seven benign vs. two pathogenic) support a benign interpretation. This consensus does not contradict ClinVar, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.887230	Disordered	0.790969	Binding	0.303	0.889	0.875								6-33443957-G-T			-5.715	Likely Benign	0.960	Likely Pathogenic	Likely Pathogenic										0.166	Likely Benign	-0.97	Neutral	0.411	Benign	0.321	Benign	5.43	Benign	0.07	Tolerated	4.32	2	0.4152	0.1793		1	0	0.4	-14.07
c.342G>C	K114N 2D AIThe SynGAP1 missense variant K114N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, while the SGM‑Consensus remains likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.754692	Disordered	0.649749	Binding	0.381	0.879	0.750											-3.851	Likely Benign	0.937	Likely Pathogenic	Ambiguous										0.045	Likely Benign	-1.41	Neutral	0.608	Possibly Damaging	0.190	Benign	3.95	Benign	0.00	Affected			0.4590	0.1877		1	0	0.4	-14.07
c.342G>T	K114N 2D AIThe SynGAP1 missense variant K114N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely benign, and Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. This conclusion is not contradicted by ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.754692	Disordered	0.649749	Binding	0.381	0.879	0.750											-3.851	Likely Benign	0.937	Likely Pathogenic	Ambiguous										0.045	Likely Benign	-1.41	Neutral	0.608	Possibly Damaging	0.190	Benign	3.95	Benign	0.00	Affected			0.4590	0.1877		1	0	0.4	-14.07
c.3537G>C	K1179N 2D AIThe SynGAP1 missense variant K1179N is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Among general in‑silico predictors, benign calls come from REVEL, PROVEAN, ESM1b, and FATHMM, whereas pathogenic calls come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy tools give a mixed picture: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Overall, the majority of high‑confidence predictions lean toward pathogenicity, and there is no ClinVar annotation to contradict this assessment. Thus, the variant is most likely pathogenic based on the current computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.637480	Disordered	0.558455	Binding	0.575	0.678	0.250											-4.764	Likely Benign	0.983	Likely Pathogenic	Likely Pathogenic										0.113	Likely Benign	-1.57	Neutral	0.975	Probably Damaging	0.766	Possibly Damaging	2.68	Benign	0.00	Affected			0.3490	0.0901		1	0	0.4	-14.07
c.3537G>T	K1179N 2D AIThe SynGAP1 K1179N missense variant is not reported in ClinVar and has no entries in gnomAD. General in silico predictors cluster into two groups: benign predictions from REVEL, PROVEAN, ESM1b, and FATHMM; pathogenic predictions from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy tools provide a mixed signal: AlphaMissense‑Optimized classifies the change as pathogenic, while the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign effect; Foldetta results are unavailable. Overall, the evidence is split, with no single consensus. Thus, the variant is currently inconclusive—neither clearly benign nor pathogenic—and does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.637480	Disordered	0.558455	Binding	0.575	0.678	0.250											-4.764	Likely Benign	0.983	Likely Pathogenic	Likely Pathogenic										0.113	Likely Benign	-1.57	Neutral	0.975	Probably Damaging	0.766	Possibly Damaging	2.68	Benign	0.00	Affected			0.3490	0.0901		1	0	0.4	-14.07
c.3543G>C	K1181N 2D AISynGAP1 missense variant K1181N is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL, PROVEAN, ESM1b, and FATHMM, while pathogenic predictions come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic, whereas the SGM‑Consensus remains Likely Benign; Foldetta results are unavailable. Overall, the balance of evidence leans toward a pathogenic effect, and this conclusion does not conflict with ClinVar status, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.622677	Disordered	0.539278	Binding	0.625	0.660	0.375											-4.872	Likely Benign	0.992	Likely Pathogenic	Likely Pathogenic										0.111	Likely Benign	-1.94	Neutral	0.999	Probably Damaging	0.977	Probably Damaging	2.65	Benign	0.02	Affected			0.2812	0.1302		1	0	0.4	-14.07
c.3543G>T	K1181N 2D AIThe SynGAP1 missense variant K1181N is not reported in ClinVar and has no gnomAD entry. Prediction tools that classify it as benign include REVEL, PROVEAN, ESM1b, and FATHMM, while polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, whereas the SGM‑Consensus again indicates Likely Benign; Foldetta results are unavailable. Overall, the predictions are mixed, with a slight edge toward pathogenicity from individual tools but a consensus leaning benign. Therefore, the variant is most likely benign based on the collective evidence, and this assessment does not contradict ClinVar status, which currently has no classification for K1181N. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.622677	Disordered	0.539278	Binding	0.625	0.660	0.375											-4.872	Likely Benign	0.992	Likely Pathogenic	Likely Pathogenic										0.111	Likely Benign	-1.94	Neutral	0.999	Probably Damaging	0.977	Probably Damaging	2.65	Benign	0.02	Affected			0.2812	0.1302		1	0	0.4	-14.07
c.3555A>C	K1185N 2D AIThe SynGAP1 missense variant K1185N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while polyPhen‑2 (HumDiv and HumVar) and AlphaMissense‑Default both predict a pathogenic outcome. The high‑accuracy consensus, SGM‑Consensus, classifies the variant as likely benign, whereas AlphaMissense‑Optimized predicts pathogenicity. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of predictions lean toward a benign interpretation, and there is no ClinVar entry to contradict this assessment. Thus, the variant is most likely benign based on current computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.566480	Disordered	0.510264	Binding	0.642	0.638	0.625											-4.345	Likely Benign	0.993	Likely Pathogenic	Likely Pathogenic										0.093	Likely Benign	-2.04	Neutral	0.999	Probably Damaging	0.995	Probably Damaging	2.68	Benign	0.12	Tolerated			0.3653	0.1145		1	0	0.4	-14.07
c.3555A>T	K1185N 2D AIThe SynGAP1 missense variant K1185N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a mixed signal: benign calls come from REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while pathogenic calls come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments further split the verdict: AlphaMissense‑Optimized predicts Pathogenic, whereas the SGM‑Consensus (majority vote) indicates Likely Benign; Foldetta results are unavailable. Overall, the balance of evidence slightly favors a benign interpretation, and there is no conflict with ClinVar status because no ClinVar claim exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.566480	Disordered	0.510264	Binding	0.642	0.638	0.625											-4.345	Likely Benign	0.993	Likely Pathogenic	Likely Pathogenic										0.093	Likely Benign	-2.04	Neutral	0.999	Probably Damaging	0.995	Probably Damaging	2.68	Benign	0.12	Tolerated			0.3653	0.1145		1	0	0.4	-14.07
c.3588G>C	K1196N 2D AIThe SynGAP1 missense variant K1196N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized predicting pathogenicity, whereas the SGM‑Consensus indicates benignity; a Foldetta stability analysis is unavailable. Overall, the majority of tools (five pathogenic vs. four benign) suggest the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.599170	Disordered	0.435699	Uncertain	0.851	0.595	0.250											-6.421	Likely Benign	0.959	Likely Pathogenic	Likely Pathogenic										0.305	Likely Benign	-1.73	Neutral	0.994	Probably Damaging	0.819	Possibly Damaging	5.37	Benign	0.04	Affected			0.3251	0.1145		1	0	0.4	-14.07
c.3588G>T	K1196N 2D AIThe SynGAP1 missense variant K1196N is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools show a split: benign calls from REVEL, PROVEAN, ESM1b, and FATHMM, while pathogenic calls come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments further divide the evidence: AlphaMissense‑Optimized predicts a pathogenic effect, whereas the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome; Foldetta stability analysis is unavailable. With no ClinVar classification to resolve the conflict, the overall computational signal is inconclusive, but the presence of a pathogenic prediction from a high‑accuracy model and the absence of a benign consensus suggest the variant is more likely pathogenic. This assessment does not contradict any ClinVar status, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.599170	Disordered	0.435699	Uncertain	0.851	0.595	0.250											-6.421	Likely Benign	0.959	Likely Pathogenic	Likely Pathogenic										0.305	Likely Benign	-1.73	Neutral	0.994	Probably Damaging	0.819	Possibly Damaging	5.37	Benign	0.04	Affected			0.3251	0.1145		1	0	0.4	-14.07
c.3618A>C	K1206N 2D AIThe SynGAP1 missense variant K1206N is not reported in ClinVar and has no entries in gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic outcome. High‑accuracy assessments further support this: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus also reports it as likely pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the preponderance of pathogenic predictions, K1206N is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.585406	Disordered	0.555819	Binding	0.893	0.569	0.375											-11.172	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.131	Likely Benign	-3.06	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.41	Pathogenic	0.01	Affected			0.3169	0.1464		1	0	0.4	-14.07
c.3618A>T	K1206N 2D AIThe SynGAP1 missense variant K1206N is not reported in ClinVar and has no entries in gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic outcome. High‑accuracy assessments further support this: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus also reports it as likely pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the preponderance of pathogenic predictions, K1206N is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.585406	Disordered	0.555819	Binding	0.893	0.569	0.375											-11.172	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.131	Likely Benign	-3.06	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.41	Pathogenic	0.01	Affected			0.3169	0.1464		1	0	0.4	-14.07
c.3645G>C	K1215N 2D AIThe SynGAP1 missense variant K1215N is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic outcome. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus also reports it as likely pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that K1215N is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.497853	Structured	0.503613	Binding	0.888	0.568	0.375											-12.569	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic										0.099	Likely Benign	-3.23	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.38	Pathogenic	0.01	Affected			0.3380	0.0901		1	0	0.4	-14.07
c.3645G>T	K1215N 2D AIThe SynGAP1 missense variant K1215N is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic outcome. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus also reports it as likely pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that K1215N is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.497853	Structured	0.503613	Binding	0.888	0.568	0.375											-12.569	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic										0.099	Likely Benign	-3.23	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.38	Pathogenic	0.01	Affected			0.3380	0.0901		1	0	0.4	-14.07
c.3696A>C	K1232N 2D AIThe SynGAP1 missense variant K1232N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: REVEL scores the variant as benign, whereas PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default all predict it to be pathogenic. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as likely pathogenic. High‑accuracy assessments are mixed: AlphaMissense‑Optimized returns an uncertain result, and Foldetta data are not available. Based on the overall evidence, the variant is most likely pathogenic, which is consistent with the lack of ClinVar annotation and gnomAD absence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.505461	Disordered	0.542907	Binding	0.894	0.535	0.125											-8.657	Likely Pathogenic	0.834	Likely Pathogenic	Ambiguous										0.167	Likely Benign	-3.72	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.10	Pathogenic	0.00	Affected			0.2913	0.1464		1	0	0.4	-14.07
c.3696A>T	K1232N 2D AIThe SynGAP1 missense variant K1232N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus—consistently predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta results are unavailable. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.505461	Disordered	0.542907	Binding	0.894	0.535	0.125											-8.657	Likely Pathogenic	0.834	Likely Pathogenic	Ambiguous										0.167	Likely Benign	-3.72	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.10	Pathogenic	0.00	Affected			0.2913	0.1464		1	0	0.4	-14.07
c.3738G>C	K1246N 2D AIThe SynGAP1 missense variant K1246N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while polyPhen‑2 (HumDiv and HumVar) and SIFT uniformly predict a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (majority vote) also indicates Likely Benign. Foldetta results are unavailable, so they do not influence the assessment. Overall, the preponderance of evidence from multiple independent predictors points to a benign effect for K1246N, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.750527	Disordered	0.375382	Uncertain	0.887	0.564	0.625											-2.506	Likely Benign	0.518	Ambiguous	Likely Benign										0.125	Likely Benign	-1.39	Neutral	0.980	Probably Damaging	0.721	Possibly Damaging	2.66	Benign	0.02	Affected			0.3316	0.0940		1	0	0.4	-14.07
c.3738G>T	K1246N 2D AIThe SynGAP1 missense variant K1246N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while polyPhen‑2 (HumDiv and HumVar) and SIFT uniformly predict a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (majority vote) also indicates Likely Benign. Foldetta results are unavailable, so they do not influence the assessment. Overall, the preponderance of evidence from multiple independent predictors points to a benign effect for K1246N, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.750527	Disordered	0.375382	Uncertain	0.887	0.564	0.625											-2.506	Likely Benign	0.518	Ambiguous	Likely Benign										0.122	Likely Benign	-1.39	Neutral	0.980	Probably Damaging	0.721	Possibly Damaging	2.66	Benign	0.02	Affected			0.3316	0.0940		1	0	0.4	-14.07
c.3765G>C	K1255N 2D AIThe SynGAP1 missense variant K1255N is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM‑Consensus as Likely Pathogenic; Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.637480	Disordered	0.417615	Uncertain	0.880	0.563	0.625											-12.586	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.210	Likely Benign	-3.99	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.85	Pathogenic	0.00	Affected			0.2993	0.1302		1	0	0.4	-14.07
c.3765G>T	K1255N 2D AIThe SynGAP1 missense variant K1255N is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM‑Consensus as Likely Pathogenic; Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the absence of benign consensus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.637480	Disordered	0.417615	Uncertain	0.880	0.563	0.625											-12.586	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.210	Likely Benign	-3.99	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.85	Pathogenic	0.00	Affected			0.2993	0.1302		1	0	0.4	-14.07
c.3780G>C	K1260N 2D AIThe SynGAP1 missense variant K1260N is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. In contrast, the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) all classify the variant as pathogenic or likely pathogenic. AlphaMissense‑Optimized is uncertain, and no Foldetta stability assessment is available. Based on the consensus of high‑accuracy predictors, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.509769	Disordered	0.625808	Binding	0.890	0.575	0.250											-9.053	Likely Pathogenic	0.915	Likely Pathogenic	Ambiguous										0.157	Likely Benign	-3.39	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.42	Pathogenic	0.00	Affected			0.3064	0.1302		1	0	0.4	-14.07
c.3780G>T	K1260N 2D AIThe SynGAP1 missense variant K1260N is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. In contrast, the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) all classify the variant as pathogenic or likely pathogenic. AlphaMissense‑Optimized is uncertain, and no Foldetta stability assessment is available. Based on the consensus of high‑accuracy predictors, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.509769	Disordered	0.625808	Binding	0.890	0.575	0.250											-9.053	Likely Pathogenic	0.915	Likely Pathogenic	Ambiguous										0.157	Likely Benign	-3.39	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.42	Pathogenic	0.00	Affected			0.3064	0.1302		1	0	0.4	-14.07
c.3864G>C	K1288N 2D AIThe SynGAP1 missense variant K1288N has no ClinVar entry and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and ESM1b, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports the variant as Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no result for this variant. High‑accuracy assessments therefore show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta as unavailable. Based on the overall distribution of predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.827927	Disordered	0.814714	Binding	0.538	0.784	0.625											-3.670	Likely Benign	0.801	Likely Pathogenic	Ambiguous										0.128	Likely Benign	-4.05	Deleterious	0.991	Probably Damaging	0.987	Probably Damaging	2.10	Pathogenic	0.00	Affected			0.3513	0.1101		1	0	0.4	-14.07
c.3864G>T	K1288N 2D AIThe SynGAP1 missense variant K1288N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect are REVEL and ESM1b, while the majority of tools predict a pathogenic effect: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports the variant as Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. High‑accuracy assessments therefore show an uncertain AlphaMissense‑Optimized prediction, a Likely Pathogenic SGM‑Consensus, and no Foldetta data. Overall, the preponderance of evidence points to a pathogenic impact, and this conclusion does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.827927	Disordered	0.814714	Binding	0.538	0.784	0.625											-3.670	Likely Benign	0.801	Likely Pathogenic	Ambiguous										0.128	Likely Benign	-4.05	Deleterious	0.991	Probably Damaging	0.987	Probably Damaging	2.10	Pathogenic	0.00	Affected			0.3513	0.1101		1	0	0.4	-14.07
c.3867G>C	K1289N 2D AIThe SynGAP1 missense variant K1289N is reported in ClinVar as “Not submitted” and is not present in gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized all classify the change as benign, while the only pathogenic call comes from SIFT. AlphaMissense‑Default is uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, SGM‑Consensus also predicts likely benign, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Based on the collective predictions, K1289N is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.733139	Disordered	0.828700	Binding	0.548	0.787	0.625											-4.244	Likely Benign	0.481	Ambiguous	Likely Benign										0.043	Likely Benign	-1.56	Neutral	0.224	Benign	0.120	Benign	2.59	Benign	0.02	Affected			0.3442	0.0940		1	0	0.4	-14.07
c.3867G>T	K1289N 2D AIThe SynGAP1 missense variant K1289N is reported in ClinVar as “Not submitted” and is not present in gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized all classify the change as benign, while the only pathogenic call comes from SIFT. AlphaMissense‑Default is uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, SGM‑Consensus also predicts likely benign, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Based on the collective predictions, K1289N is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.733139	Disordered	0.828700	Binding	0.548	0.787	0.625											-4.244	Likely Benign	0.481	Ambiguous	Likely Benign										0.043	Likely Benign	-1.56	Neutral	0.224	Benign	0.120	Benign	2.59	Benign	0.02	Affected			0.3442	0.0940		1	0	0.4	-14.07
c.414A>C	K138N 2D AIThe SynGAP1 missense variant K138N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas a majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The remaining tool, ESM1b, yields an uncertain result. High‑accuracy assessments further support a deleterious interpretation: AlphaMissense‑Optimized is pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also favors pathogenicity. Foldetta, a protein‑folding stability predictor, has no available result for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that K138N is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.590140	Disordered	0.619482	Binding	0.349	0.901	0.375											-7.920	In-Between	0.999	Likely Pathogenic	Likely Pathogenic										0.093	Likely Benign	-2.77	Deleterious	0.700	Possibly Damaging	0.310	Benign	3.56	Benign	0.01	Affected			0.3438	0.1627		1	0	0.4	-14.07
c.414A>T	K138N 2D AIThe SynGAP1 missense variant K138N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas a majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The remaining tool, ESM1b, yields an uncertain result. High‑accuracy assessments further support a deleterious interpretation: AlphaMissense‑Optimized is pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also favors pathogenicity. Foldetta, a protein‑folding stability predictor, has no available result for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that K138N is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.590140	Disordered	0.619482	Binding	0.349	0.901	0.375											-7.920	In-Between	0.999	Likely Pathogenic	Likely Pathogenic										0.093	Likely Benign	-2.77	Deleterious	0.700	Possibly Damaging	0.310	Benign	3.56	Benign	0.01	Affected			0.3438	0.1627		1	0	0.4	-14.07
c.426A>C	K142N 2D AIThe SynGAP1 missense variant K142N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus also indicates Likely Pathogenic. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of computational evidence points to a pathogenic effect, and this conclusion does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.461924	Structured	0.558796	Binding	0.374	0.859	0.500											-12.169	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic										0.097	Likely Benign	-3.13	Deleterious	0.700	Possibly Damaging	0.383	Benign	3.47	Benign	0.00	Affected			0.3586	0.1437		1	0	0.4	-14.07
c.426A>T	K142N 2D AIThe SynGAP1 missense variant K142N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus also indicates Likely Pathogenic. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of computational evidence points to a pathogenic effect, and this conclusion does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.461924	Structured	0.558796	Binding	0.374	0.859	0.500											-12.169	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic										0.096	Likely Benign	-3.13	Deleterious	0.700	Possibly Damaging	0.383	Benign	3.47	Benign	0.00	Affected			0.3586	0.1437		1	0	0.4	-14.07
c.435G>C	K145N 2D AIThe SynGAP1 missense variant K145N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic). High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic and the SGM‑Consensus as Likely Pathogenic; the Foldetta protein‑folding stability analysis is unavailable. Overall, the majority of evidence points toward a pathogenic impact for K145N, and this conclusion does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.671169	Disordered	0.516174	Binding	0.321	0.835	0.625											-8.718	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic										0.109	Likely Benign	-2.76	Deleterious	0.700	Possibly Damaging	0.383	Benign	3.65	Benign	0.00	Affected			0.3430	0.1832		1	0	0.4	-14.07
c.435G>T	K145N 2D AIThe SynGAP1 missense variant K145N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign predictions come from REVEL (score 0.45), polyPhen‑2 HumVar (benign), and FATHMM (benign). Pathogenic predictions arise from PROVEAN (deleterious), polyPhen‑2 HumDiv (probably damaging), SIFT (deleterious), ESM1b (damaging), AlphaMissense‑Default (pathogenic), and AlphaMissense‑Optimized (pathogenic). The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments reinforce this: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus also indicates Likely Pathogenic. Foldetta results are unavailable. Overall, the majority of evidence points to a pathogenic effect, and this is consistent with the lack of ClinVar annotation; there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.671169	Disordered	0.516174	Binding	0.321	0.835	0.625											-8.718	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic										0.109	Likely Benign	-2.76	Deleterious	0.700	Possibly Damaging	0.383	Benign	3.65	Benign	0.00	Affected			0.3430	0.1832		1	0	0.4	-14.07
c.447A>C	K149N 2D AIThe SynGAP1 missense variant K149N is not reported in ClinVar and has no entry in gnomAD, indicating it is not catalogued in these databases. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. In contrast, tools that predict a pathogenic effect are PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy consensus, SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a majority pathogenic vote (3 pathogenic vs. 1 benign) and is labeled “Likely Pathogenic.” AlphaMissense‑Optimized independently predicts pathogenicity. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, is not available for this variant. Overall, the majority of computational evidence points to a pathogenic impact, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.562014	Disordered	0.501681	Binding	0.302	0.839	0.625											-9.275	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.121	Likely Benign	-2.85	Deleterious	0.141	Benign	0.123	Benign	3.56	Benign	0.00	Affected			0.4427	0.1559		1	0	0.4	-14.07
c.447A>T	K149N 2D AIThe SynGAP1 missense variant K149N is not reported in ClinVar and has no entries in gnomAD, indicating it is not catalogued in these databases. Functional prediction tools show a split: benign predictions come from REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM, whereas pathogenic predictions arise from PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments reinforce the pathogenic signal: AlphaMissense‑Optimized predicts pathogenic, and the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—also indicates likely pathogenic. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a pathogenic effect for K149N, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.562014	Disordered	0.501681	Binding	0.302	0.839	0.625											-9.275	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.121	Likely Benign	-2.85	Deleterious	0.141	Benign	0.123	Benign	3.56	Benign	0.00	Affected			0.4427	0.1559		1	0	0.4	-14.07
c.534G>C	K178N 2D AIThe SynGAP1 missense variant K178N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that classify the variant as benign include REVEL and FATHMM, whereas the remaining tools—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN)—all predict it to be pathogenic or likely pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus reports Likely Pathogenic, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) is unavailable for this variant. Based on the preponderance of pathogenic predictions, K178N is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.497853	Structured	0.455271	Uncertain	0.354	0.622	0.375											-12.137	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic										0.131	Likely Benign	-3.32	Deleterious	0.971	Probably Damaging	0.598	Possibly Damaging	3.86	Benign	0.01	Affected			0.4503	0.1321		1	0	0.4	-14.07
c.534G>T	K178N 2D AIThe SynGAP1 missense variant K178N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect are REVEL and FATHMM, while the remaining tools—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic outcome. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized classifies the variant as pathogenic, the SGM‑Consensus indicates it is likely pathogenic, and Foldetta’s protein‑folding stability analysis is unavailable. Based on the preponderance of pathogenic predictions and the high‑accuracy tools’ results, the variant is most likely pathogenic; this conclusion is not contradicted by any ClinVar status, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.497853	Structured	0.455271	Uncertain	0.354	0.622	0.375											-12.137	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic										0.131	Likely Benign	-3.32	Deleterious	0.971	Probably Damaging	0.598	Possibly Damaging	3.86	Benign	0.01	Affected			0.4503	0.1321		1	0	0.4	-14.07
c.621G>C	K207N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K207N missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM, whereas a majority of tools predict a pathogenic impact: SGM‑Consensus, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX, Rosetta, and Foldetta provide uncertain or inconclusive results and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicating likely pathogenic, while Foldetta’s stability prediction is unavailable. Overall, the preponderance of evidence points to a pathogenic effect for K207N, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.374039	Structured	0.406823	Uncertain	0.847	0.359	0.125											-12.881	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	0.72	Ambiguous	0.1	1.48	Ambiguous	1.10	Ambiguous	1.00	Destabilizing	0.123	Likely Benign	-3.54	Deleterious	0.995	Probably Damaging	0.829	Possibly Damaging	3.98	Benign	0.07	Tolerated			0.3184	0.2335		1	0	0.4	-14.07
c.621G>T	K207N 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K207N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, SIFT, and FATHMM, whereas pathogenic predictions arise from premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Pathogenic. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts Pathogenic, and the SGM Consensus (majority vote) also predicts Pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is inconclusive. Overall, the preponderance of evidence indicates that K207N is most likely pathogenic, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.374039	Structured	0.406823	Uncertain	0.847	0.359	0.125											-12.881	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	0.72	Ambiguous	0.1	1.48	Ambiguous	1.10	Ambiguous	1.00	Destabilizing	0.124	Likely Benign	-3.54	Deleterious	0.995	Probably Damaging	0.829	Possibly Damaging	3.98	Benign	0.07	Tolerated			0.3184	0.2335		1	0	0.4	-14.07
c.687A>C	K229N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K229N missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are limited to FATHMM, whereas the remaining tools—SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. Four tools (FoldX, Rosetta, Foldetta, premPS) return uncertain results and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of evidence points to a pathogenic effect. The variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.179055	Structured	0.310912	Uncertain	0.843	0.306	0.000											-13.620	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	0.82	Ambiguous	0.1	0.64	Ambiguous	0.73	Ambiguous	0.61	Ambiguous	0.590	Likely Pathogenic	-3.79	Deleterious	0.998	Probably Damaging	0.987	Probably Damaging	5.83	Benign	0.01	Affected			0.3682	0.1013		1	0	0.4	-14.07
c.687A>T	K229N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K229N missense variant is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only FATHMM, whereas the remaining nine tools—REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—consistently predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support this view: AlphaMissense‑Optimized is pathogenic; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is labeled Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, is uncertain and therefore not considered evidence for or against pathogenicity. Based on the collective predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.179055	Structured	0.310912	Uncertain	0.843	0.306	0.000											-13.620	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	0.82	Ambiguous	0.1	0.64	Ambiguous	0.73	Ambiguous	0.61	Ambiguous	0.588	Likely Pathogenic	-3.79	Deleterious	0.998	Probably Damaging	0.987	Probably Damaging	5.83	Benign	0.01	Affected			0.3682	0.1013		1	0	0.4	-14.07
c.723A>C	K241N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K241N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only FATHMM, whereas the remaining tools—REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is inconclusive. Based on the collective predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.196879	Structured	0.349250	Uncertain	0.797	0.347	0.000											-10.198	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	0.92	Ambiguous	0.1	1.13	Ambiguous	1.03	Ambiguous	0.89	Ambiguous	0.663	Likely Pathogenic	-4.23	Deleterious	0.995	Probably Damaging	0.829	Possibly Damaging	5.81	Benign	0.03	Affected			0.3426	0.1872		1	0	0.4	-14.07
c.723A>T	K241N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K241N is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only FATHMM, whereas the majority of tools predict a pathogenic impact: REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain results are reported for FoldX, Rosetta, Foldetta, and premPS and are not used as evidence. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta as uncertain. Based on the overall consensus of the available predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.196879	Structured	0.349250	Uncertain	0.797	0.347	0.000											-10.198	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	0.92	Ambiguous	0.1	1.13	Ambiguous	1.03	Ambiguous	0.89	Ambiguous	0.663	Likely Pathogenic	-4.23	Deleterious	0.995	Probably Damaging	0.829	Possibly Damaging	5.81	Benign	0.03	Affected			0.3426	0.1872		1	0	0.4	-14.07
c.753G>C	K251N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K251N is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM (nine tools). Only AlphaMissense‑Default predicts a pathogenic outcome, while ESM1b and AlphaMissense‑Optimized are uncertain. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a benign consensus; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign stability. Overall, the preponderance of evidence indicates that K251N is most likely benign, and this conclusion does not contradict the current ClinVar status, which has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		PH	0.447574	Structured	0.226632	Uncertain	0.758	0.312	0.125											-7.978	In-Between	0.930	Likely Pathogenic	Ambiguous	0.29	Likely Benign	0.1	0.21	Likely Benign	0.25	Likely Benign	0.32	Likely Benign	0.298	Likely Benign	-1.29	Neutral	0.384	Benign	0.070	Benign	5.73	Benign	0.39	Tolerated			0.3848	0.1196		1	0	0.4	-14.07
c.753G>T	K251N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K251N is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM (nine tools). Only AlphaMissense‑Default predicts a pathogenic outcome, while ESM1b and AlphaMissense‑Optimized are uncertain. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a benign consensus; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign stability. Overall, the preponderance of evidence indicates that K251N is most likely benign, and this conclusion does not contradict the current ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		PH	0.447574	Structured	0.226632	Uncertain	0.758	0.312	0.125											-7.978	In-Between	0.930	Likely Pathogenic	Ambiguous	0.29	Likely Benign	0.1	0.21	Likely Benign	0.25	Likely Benign	0.32	Likely Benign	0.298	Likely Benign	-1.29	Neutral	0.384	Benign	0.070	Benign	5.73	Benign	0.39	Tolerated			0.3848	0.1196		1	0	0.4	-14.07
c.762G>C	K254N 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K254N is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Functional prediction tools that classify the variant as benign include polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. The majority of other in silico predictors—REVEL, premPS, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—indicate a pathogenic effect. Stability‑based methods FoldX, Rosetta, and Foldetta returned uncertain results and are therefore not considered evidence for or against pathogenicity. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as likely pathogenic, and Foldetta as unavailable. Overall, the preponderance of evidence supports a pathogenic classification, which contradicts the current ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.513880	Disordered	0.207751	Uncertain	0.799	0.285	0.375					Uncertain		1				-13.306	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.73	Ambiguous	0.2	1.87	Ambiguous	1.30	Ambiguous	1.19	Destabilizing	0.757	Likely Pathogenic	-4.23	Deleterious	0.384	Benign	0.070	Benign	5.93	Benign	0.01	Affected	3.39	15	0.3200	0.1488		1	0	0.4	-14.07	215.3	-21.0	-1.0	1.7	0.2	0.3		X						Potentially Pathogenic	The amino group of Lys254, located in an α-β loop connecting the PH and C2 domains (res. Lys251-Arg258), forms salt bridges with the carboxylate groups of Glu244 and Asp684. Since the neutral carboxamide group of the Asn254 side chain cannot form salt bridges with acidic residues, the residue swap potentially weakens the tertiary structure assembly and/or influences the loop positioning. Regardless, in both the variant and WT simulations, all hydrogen bonds formed by the residue’s side chain were broken, and the residue rotated outwards. The partially α helical conformation of the loop, which extends to a nearby α helix (res. Met414-Asn426), is dynamic, making it unclear if the mutation affects it.
c.762G>T	K254N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K254N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that classify the variant as benign include polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that predict a pathogenic effect are REVEL, premPS, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus score, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is “Likely Pathogenic” (3 pathogenic vs. 1 benign). High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. No evidence from FoldX or Rosetta alone is conclusive. Based on the overall pattern of predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant is not currently catalogued in ClinVar. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.513880	Disordered	0.207751	Uncertain	0.799	0.285	0.375											-13.306	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.73	Ambiguous	0.2	1.87	Ambiguous	1.30	Ambiguous	1.19	Destabilizing	0.757	Likely Pathogenic	-4.23	Deleterious	0.384	Benign	0.070	Benign	5.93	Benign	0.01	Affected	3.39	15	0.3200	0.1488		1	0	0.4	-14.07	215.3	-21.0	-1.0	1.7	0.2	0.3		X						Potentially Pathogenic	The amino group of Lys254, located in an α-β loop connecting the PH and C2 domains (res. Lys251-Arg258), forms salt bridges with the carboxylate groups of Glu244 and Asp684. Since the neutral carboxamide group of the Asn254 side chain cannot form salt bridges with acidic residues, the residue swap potentially weakens the tertiary structure assembly and/or influences the loop positioning. Regardless, in both the variant and WT simulations, all hydrogen bonds formed by the residue’s side chain were broken, and the residue rotated outwards. The partially α helical conformation of the loop, which extends to a nearby α helix (res. Met414-Asn426), is dynamic, making it unclear if the mutation affects it.
c.795G>C	K265N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K265N missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL and Rosetta, whereas the majority of algorithms predict a pathogenic outcome: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic). Uncertain results are reported by FoldX, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as Likely Pathogenic, and Foldetta as uncertain. Based on the overall consensus of the available predictions, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.209395	Structured	0.309758	Uncertain	0.936	0.275	0.000											-8.759	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic	0.98	Ambiguous	0.1	0.16	Likely Benign	0.57	Ambiguous	0.85	Ambiguous	0.350	Likely Benign	-3.26	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.86	Pathogenic	0.03	Affected			0.3691	0.1158		1	0	0.4	-14.07
c.795G>T	K265N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K265N missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL and Rosetta, while the majority of algorithms predict a pathogenic outcome: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic). Uncertain or inconclusive results are reported only for FoldX, Foldetta, and premPS, and are treated as unavailable evidence. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as Likely Pathogenic, and Foldetta as uncertain. Based on the overall consensus of the available predictions, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status (none is assigned). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.209395	Structured	0.309758	Uncertain	0.936	0.275	0.000											-8.759	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic	0.98	Ambiguous	0.1	0.16	Likely Benign	0.57	Ambiguous	0.85	Ambiguous	0.351	Likely Benign	-3.26	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.86	Pathogenic	0.03	Affected			0.3691	0.1158		1	0	0.4	-14.07
c.831G>C	K277N 2D AIThe SynGAP1 missense variant K277N is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that classify the variant as benign include FoldX, Rosetta, Foldetta, and premPS. Tools that predict pathogenicity are SGM‑Consensus (Likely Pathogenic), REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic, SGM‑Consensus as Likely Pathogenic (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta as Benign. No predictions are missing or inconclusive. Overall, the majority of tools (10/14) predict pathogenicity, whereas four tools predict benign. Therefore, the variant is most likely pathogenic based on current computational evidence, and this assessment does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.061840	Structured	0.321811	Uncertain	0.649	0.247	0.250											-9.646	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	-0.07	Likely Benign	0.4	0.08	Likely Benign	0.01	Likely Benign	0.46	Likely Benign	0.572	Likely Pathogenic	-4.60	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.83	Pathogenic	0.03	Affected			0.3265	0.0568		1	0	0.4	-14.07
c.831G>T	K277N 2D AIThe SynGAP1 missense variant K277N is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that indicate a benign effect include FoldX, Rosetta, Foldetta, and premPS. In contrast, the majority of tools predict a pathogenic impact: SGM‑Consensus (Likely Pathogenic), REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy methods give a mixed picture: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is also likely pathogenic; Foldetta, a protein‑folding stability predictor, reports a benign effect. Overall, the preponderance of evidence (10 pathogenic vs. 4 benign predictions) points to a pathogenic classification. This conclusion is not contradicted by ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.061840	Structured	0.321811	Uncertain	0.649	0.247	0.250											-9.646	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	-0.07	Likely Benign	0.4	0.08	Likely Benign	0.01	Likely Benign	0.46	Likely Benign	0.572	Likely Pathogenic	-4.60	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.83	Pathogenic	0.03	Affected			0.3265	0.0568		1	0	0.4	-14.07
c.834G>C	K278N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K278N is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify it as benign include REVEL, FoldX, Rosetta, premPS, and SIFT, whereas pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy methods give mixed results: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) predicts benign. Overall, the majority of tools support a pathogenic effect, so the variant is most likely pathogenic; this is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.120615	Structured	0.310130	Uncertain	0.748	0.253	0.125											-10.611	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic	0.40	Likely Benign	0.0	0.05	Likely Benign	0.23	Likely Benign	0.44	Likely Benign	0.255	Likely Benign	-4.51	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.81	Pathogenic	0.07	Tolerated			0.3071	0.0568		1	0	0.4	-14.07
c.834G>T	K278N 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K278N is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools that classify the variant as benign include REVEL, FoldX, Rosetta, premPS, and SIFT, whereas tools that predict pathogenicity are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments further show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. With a majority of evidence pointing to deleterious effects and no ClinVar annotation to contradict, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.120615	Structured	0.310130	Uncertain	0.748	0.253	0.125											-10.611	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic	0.40	Likely Benign	0.0	0.05	Likely Benign	0.23	Likely Benign	0.44	Likely Benign	0.255	Likely Benign	-4.51	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.81	Pathogenic	0.07	Tolerated			0.3071	0.0568		1	0	0.4	-14.07
c.891G>C	K297N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K297N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only REVEL, whereas the majority of tools (premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) predict a pathogenic impact. FoldX, Rosetta, and Foldetta provide uncertain or inconclusive stability results and are therefore not considered evidence for or against pathogenicity. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as Likely Pathogenic, and Foldetta as uncertain. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.422041	Structured	0.272593	Uncertain	0.880	0.285	0.375											-11.328	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	1.08	Ambiguous	0.1	1.60	Ambiguous	1.34	Ambiguous	1.15	Destabilizing	0.253	Likely Benign	-4.31	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.61	Pathogenic	0.01	Affected			0.3797	0.2265		1	0	0.4	-14.07
c.891G>T	K297N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K297N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only REVEL, whereas the majority of tools (premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) predict a pathogenic impact. FoldX, Rosetta, and Foldetta provide uncertain or inconclusive stability results and are therefore not considered evidence for or against pathogenicity. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as Likely Pathogenic, and Foldetta as uncertain. Based on the preponderance of pathogenic predictions and the lack of benign consensus, K297N is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.422041	Structured	0.272593	Uncertain	0.880	0.285	0.375											-11.328	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	1.08	Ambiguous	0.1	1.60	Ambiguous	1.34	Ambiguous	1.15	Destabilizing	0.253	Likely Benign	-4.31	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.61	Pathogenic	0.01	Affected			0.3797	0.2265		1	0	0.4	-14.07
c.999A>C	K333N 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K333N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split opinion: benign predictions come from REVEL, FoldX, Rosetta, and SIFT, whereas pathogenic predictions are reported by PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). The high‑accuracy subset yields contrasting results: AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus also indicates Likely Pathogenic, while Foldetta (combining FoldX‑MD and Rosetta stability outputs) predicts benign. premPS is inconclusive. Overall, the majority of tools lean toward pathogenicity, and the high‑accuracy predictions are not uniformly supportive of benign status. Therefore, K333N is most likely pathogenic, and this assessment does not contradict any ClinVar annotation because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.311707	Structured	0.330781	Uncertain	0.537	0.447	0.500											-11.821	Likely Pathogenic	0.989	Likely Pathogenic	Likely Pathogenic	0.30	Likely Benign	0.1	0.42	Likely Benign	0.36	Likely Benign	0.55	Ambiguous	0.359	Likely Benign	-4.03	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.91	Pathogenic	0.13	Tolerated			0.3267	0.1315		1	0	0.4	-14.07
c.999A>T	K333N 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K333N has no ClinVar record and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, and SIFT, whereas a larger group predicts pathogenicity: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). The high‑accuracy methods give mixed results: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates likely pathogenic, whereas Foldetta (combining FoldX‑MD and Rosetta outputs) reports a benign stability change. premPS is inconclusive and is treated as unavailable. Overall, the majority of evidence points to a pathogenic effect, and this assessment does not contradict any ClinVar annotation because none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.311707	Structured	0.330781	Uncertain	0.537	0.447	0.500											-11.821	Likely Pathogenic	0.989	Likely Pathogenic	Likely Pathogenic	0.30	Likely Benign	0.1	0.42	Likely Benign	0.36	Likely Benign	0.55	Ambiguous	0.366	Likely Benign	-4.03	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.91	Pathogenic	0.13	Tolerated			0.3267	0.1315		1	0	0.4	-14.07
c.1019C>G	A340G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A340G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Only FATHMM predicts a pathogenic outcome. Stability‑based methods (FoldX, Rosetta, Foldetta) are inconclusive, so they provide no evidence for or against pathogenicity. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus as likely benign, and Foldetta as uncertain. Overall, the majority of reliable predictors indicate a benign effect, and there is no ClinVar annotation to contradict this assessment. Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.390993	Structured	0.410781	Uncertain	0.558	0.485	0.250											-3.763	Likely Benign	0.099	Likely Benign	Likely Benign	0.66	Ambiguous	0.2	1.44	Ambiguous	1.05	Ambiguous	0.50	Likely Benign	0.044	Likely Benign	-0.34	Neutral	0.267	Benign	0.127	Benign	1.92	Pathogenic	0.42	Tolerated			0.2355	0.4470		1	0	-2.2	-14.03
c.1033C>G	L345V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 L345V missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL, Rosetta, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and polyPhen‑2 HumVar. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also leans toward benign. Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is inconclusive. Overall, the majority of evidence points to a benign impact for this variant, and this conclusion does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.260850	Structured	0.354989	Uncertain	0.936	0.478	0.125											-6.594	Likely Benign	0.131	Likely Benign	Likely Benign	1.31	Ambiguous	0.0	0.18	Likely Benign	0.75	Ambiguous	0.92	Ambiguous	0.126	Likely Benign	-1.96	Neutral	0.802	Possibly Damaging	0.277	Benign	1.77	Pathogenic	0.06	Tolerated			0.1411	0.3455		2	1	0.4	-14.03
c.1039A>T	T347S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T347S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Only FATHMM predicts a pathogenic outcome. Stability‑based methods (FoldX, Rosetta, Foldetta) are inconclusive, so they provide no evidence for or against pathogenicity. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely benign, and Foldetta as uncertain. Overall, the majority of reliable predictors indicate a benign effect, and there is no ClinVar annotation to contradict this assessment. Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.268042	Structured	0.349915	Uncertain	0.951	0.434	0.000											-3.342	Likely Benign	0.090	Likely Benign	Likely Benign	0.65	Ambiguous	0.1	0.82	Ambiguous	0.74	Ambiguous	-0.10	Likely Benign	0.104	Likely Benign	0.63	Neutral	0.002	Benign	0.001	Benign	1.75	Pathogenic	0.86	Tolerated			0.3205	0.4707		1	1	-0.1	-14.03
c.1040C>G	T347S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T347S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Only FATHMM predicts a pathogenic outcome. Stability‑based methods (FoldX, Rosetta, Foldetta) are inconclusive, so they provide no evidence for or against pathogenicity. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely benign, and Foldetta as uncertain. Overall, the majority of reliable predictors indicate a benign effect, and there is no ClinVar annotation to contradict this assessment. Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.268042	Structured	0.349915	Uncertain	0.951	0.434	0.000											-3.342	Likely Benign	0.090	Likely Benign	Likely Benign	0.65	Ambiguous	0.1	0.82	Ambiguous	0.74	Ambiguous	-0.10	Likely Benign	0.054	Likely Benign	0.63	Neutral	0.002	Benign	0.001	Benign	1.75	Pathogenic	0.86	Tolerated			0.3205	0.4707		1	1	-0.1	-14.03
c.1052C>G	A351G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 A351G missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Functional prediction tools that agree on a benign effect include REVEL, FoldX, polyPhen‑2 HumVar, AlphaMissense‑Default, AlphaMissense‑Optimized, and ESM1b. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, SIFT, and FATHMM. Predictions that are uncertain or inconclusive are Rosetta, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (two benign vs two pathogenic), and Foldetta is uncertain. Taken together, the majority of available predictions lean toward a benign impact, and this assessment does not contradict the lack of ClinVar annotation. Thus, the variant is most likely benign based on current computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.216401	Structured	0.362025	Uncertain	0.925	0.342	0.000											-4.983	Likely Benign	0.089	Likely Benign	Likely Benign	0.39	Likely Benign	0.0	1.04	Ambiguous	0.72	Ambiguous	0.55	Ambiguous	0.041	Likely Benign	-2.53	Deleterious	0.688	Possibly Damaging	0.138	Benign	1.77	Pathogenic	0.04	Affected			0.2298	0.4737		1	0	-2.2	-14.03
c.1054A>T	T352S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T352S is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools largely agree on a benign effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only FATHMM predicts a pathogenic outcome. The high‑accuracy consensus methods reinforce the benign assessment: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields “Likely Benign”; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also reports a benign effect. No predictions or stability results are missing or inconclusive. Based on the overwhelming agreement among the majority of tools and the high‑accuracy methods, the variant is most likely benign, and this conclusion does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.137348	Structured	0.367886	Uncertain	0.926	0.329	0.000											-1.670	Likely Benign	0.062	Likely Benign	Likely Benign	-0.09	Likely Benign	0.0	0.26	Likely Benign	0.09	Likely Benign	-0.01	Likely Benign	0.098	Likely Benign	0.57	Neutral	0.002	Benign	0.002	Benign	1.81	Pathogenic	1.00	Tolerated			0.3583	0.4880		1	1	-0.1	-14.03
c.1055C>G	T352S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T352S is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools largely agree on a benign effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only FATHMM predicts a pathogenic outcome. The high‑accuracy consensus methods reinforce the benign assessment: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields “Likely Benign”; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also reports a benign effect. No predictions or stability results are missing or inconclusive. Based on the overwhelming agreement among the majority of tools and the high‑accuracy methods, the variant is most likely benign, and this conclusion does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.137348	Structured	0.367886	Uncertain	0.926	0.329	0.000											-1.670	Likely Benign	0.062	Likely Benign	Likely Benign	-0.09	Likely Benign	0.0	0.26	Likely Benign	0.09	Likely Benign	-0.01	Likely Benign	0.104	Likely Benign	0.57	Neutral	0.002	Benign	0.002	Benign	1.81	Pathogenic	1.00	Tolerated			0.3583	0.4880		1	1	-0.1	-14.03
c.1057C>G	L353V 2D AISynGAP1 missense variant L353V is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools predicting pathogenicity are FoldX and FATHMM, while Rosetta gives an uncertain result. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as likely benign. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. Overall, the balance of evidence favors a benign effect; this conclusion does not contradict the ClinVar status, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.137348	Structured	0.373584	Uncertain	0.926	0.315	0.000											-2.100	Likely Benign	0.078	Likely Benign	Likely Benign	3.08	Destabilizing	0.9	1.48	Ambiguous	2.28	Destabilizing	-0.45	Likely Benign	0.074	Likely Benign	1.54	Neutral	0.002	Benign	0.002	Benign	1.46	Pathogenic	0.89	Tolerated			0.1567	0.3829		2	1	0.4	-14.03
c.1061C>G	A354G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A354G is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and FATHMM. Predictions marked uncertain (Rosetta, Foldetta, premPS) are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely benign, while Foldetta’s stability analysis is inconclusive. Overall, the majority of evidence points to a benign impact for A354G, and this conclusion does not contradict any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.203355	Structured	0.381329	Uncertain	0.882	0.335	0.125											-4.285	Likely Benign	0.113	Likely Benign	Likely Benign	0.41	Likely Benign	0.0	1.24	Ambiguous	0.83	Ambiguous	0.65	Ambiguous	0.037	Likely Benign	-1.87	Neutral	0.146	Benign	0.038	Benign	1.75	Pathogenic	0.05	Affected			0.2563	0.4777		1	0	-2.2	-14.03
c.1075A>T	T359S 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant T359S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score. Only FATHMM predicts a pathogenic outcome, while FoldX, Rosetta, Foldetta, and premPS are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also favors benign. Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, is uncertain. Overall, the majority of evidence points to a benign effect, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.281712	Structured	0.414952	Uncertain	0.939	0.480	0.250											-4.624	Likely Benign	0.091	Likely Benign	Likely Benign	0.50	Ambiguous	0.0	0.73	Ambiguous	0.62	Ambiguous	0.66	Ambiguous	0.100	Likely Benign	-1.87	Neutral	0.146	Benign	0.024	Benign	1.76	Pathogenic	0.27	Tolerated			0.3637	0.4996		1	1	-0.1	-14.03
c.1080G>C	E360D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E360D is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, premPS, and SIFT. In contrast, a majority of tools predict a pathogenic impact: SGM‑Consensus (Likely Pathogenic), PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX, Rosetta, and Foldetta give uncertain results and are therefore not considered evidence for either side. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is pathogenic, SGM‑Consensus remains Likely Pathogenic, while Foldetta is uncertain. Overall, the preponderance of evidence points to a pathogenic effect for E360D. This conclusion is not contradicted by ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.250310	Structured	0.421183	Uncertain	0.955	0.498	0.250											-9.383	Likely Pathogenic	0.971	Likely Pathogenic	Likely Pathogenic	1.00	Ambiguous	0.0	0.63	Ambiguous	0.82	Ambiguous	0.11	Likely Benign	0.290	Likely Benign	-2.76	Deleterious	0.994	Probably Damaging	0.970	Probably Damaging	1.77	Pathogenic	0.07	Tolerated			0.2339	0.5735		3	2	0.0	-14.03
c.1080G>T	E360D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E360D is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that classify the variant as benign include REVEL, premPS, and SIFT, whereas the majority of tools predict it to be pathogenic: SGM‑Consensus (Likely Pathogenic), PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX, Rosetta, and Foldetta give uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as Likely Pathogenic, and Foldetta as uncertain. Based on the overall consensus of the available predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.250310	Structured	0.421183	Uncertain	0.955	0.498	0.250											-9.383	Likely Pathogenic	0.971	Likely Pathogenic	Likely Pathogenic	1.00	Ambiguous	0.0	0.63	Ambiguous	0.82	Ambiguous	0.11	Likely Benign	0.290	Likely Benign	-2.76	Deleterious	0.994	Probably Damaging	0.970	Probably Damaging	1.77	Pathogenic	0.07	Tolerated			0.2339	0.5735		3	2	0.0	-14.03
c.1096A>T	T366S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T366S is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only FATHMM predicts a pathogenic outcome, while Rosetta and Foldetta are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Benign, and Foldetta as uncertain. Overall, the majority of evidence points to a benign effect. There is no conflict with ClinVar status, as the variant is not yet classified in that database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.414856	Structured	0.441902	Uncertain	0.897	0.642	0.250											-3.273	Likely Benign	0.085	Likely Benign	Likely Benign	0.13	Likely Benign	0.1	0.92	Ambiguous	0.53	Ambiguous	0.27	Likely Benign	0.058	Likely Benign	0.00	Neutral	0.005	Benign	0.001	Benign	1.73	Pathogenic	0.78	Tolerated			0.3549	0.4878		1	1	-0.1	-14.03
c.1097C>G	T366S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T366S is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only FATHMM predicts a pathogenic outcome, while Rosetta and Foldetta are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Benign, and Foldetta as uncertain. Overall, the majority of evidence points to a benign effect. There is no conflict with ClinVar status, as the variant is not yet classified in that database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.414856	Structured	0.441902	Uncertain	0.897	0.642	0.250											-3.273	Likely Benign	0.085	Likely Benign	Likely Benign	0.13	Likely Benign	0.1	0.92	Ambiguous	0.53	Ambiguous	0.27	Likely Benign	0.051	Likely Benign	0.00	Neutral	0.005	Benign	0.001	Benign	1.73	Pathogenic	0.78	Tolerated			0.3549	0.4878		1	1	-0.1	-14.03
c.1099C>G	L367V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L367V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Only FATHMM predicts a pathogenic outcome. Stability‑based methods (FoldX, Rosetta, Foldetta) are inconclusive, so they provide no evidence for or against pathogenicity. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus as likely benign, and Foldetta as uncertain. Overall, the preponderance of evidence points to a benign effect for L367V, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.370445	Structured	0.441805	Uncertain	0.790	0.657	0.250											-2.383	Likely Benign	0.066	Likely Benign	Likely Benign	1.48	Ambiguous	0.2	1.72	Ambiguous	1.60	Ambiguous	0.15	Likely Benign	0.040	Likely Benign	0.19	Neutral	0.410	Benign	0.104	Benign	1.67	Pathogenic	0.13	Tolerated			0.2321	0.3285		2	1	0.4	-14.03
c.1105A>T	T369S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T369S is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only FATHMM predicts a pathogenic outcome. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign”; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts benign. No predictions or stability results are missing or inconclusive. Based on the collective evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.468512	Structured	0.437011	Uncertain	0.417	0.707	0.500											-2.018	Likely Benign	0.071	Likely Benign	Likely Benign	-0.07	Likely Benign	0.1	0.34	Likely Benign	0.14	Likely Benign	0.18	Likely Benign	0.097	Likely Benign	-0.81	Neutral	0.001	Benign	0.001	Benign	1.78	Pathogenic	0.39	Tolerated			0.3746	0.4994		1	1	-0.1	-14.03
c.1196C>G	A399G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A399G is not reported in ClinVar and is absent from gnomAD. Across a panel of in silico predictors, all available pathogenicity scores classify the substitution as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts pathogenicity. Uncertain results from FoldX, Rosetta, Foldetta, and premPS are treated as unavailable. High‑accuracy assessments reinforce the benign prediction: AlphaMissense‑Optimized is benign; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates benign. Foldetta, which integrates FoldX‑MD and Rosetta outputs, is inconclusive and therefore not considered evidence. Consequently, the variant is most likely benign, and this assessment does not contradict any ClinVar annotation (none present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.394753	Structured	0.407674	Uncertain	0.939	0.490	0.125											-6.513	Likely Benign	0.215	Likely Benign	Likely Benign	1.03	Ambiguous	0.1	1.77	Ambiguous	1.40	Ambiguous	0.74	Ambiguous	0.153	Likely Benign	-1.59	Neutral	0.062	Benign	0.024	Benign	5.39	Benign	0.13	Tolerated			0.2174	0.4532		1	0	-2.2	-14.03
c.1204C>G	L402V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L402V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: REVEL, premPS, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, PROVEAN, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized is benign; the SGM‑Consensus (derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also reports a benign outcome. Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, yields an uncertain result and is therefore not considered evidence for pathogenicity. In summary, all available predictions support a benign classification for the L402V variant, and this conclusion does not contradict the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.243554	Structured	0.431978	Uncertain	0.961	0.383	0.000											-3.467	Likely Benign	0.105	Likely Benign	Likely Benign	1.91	Ambiguous	0.1	0.78	Ambiguous	1.35	Ambiguous	-0.11	Likely Benign	0.203	Likely Benign	0.18	Neutral	0.004	Benign	0.004	Benign	4.01	Benign	0.29	Tolerated			0.1807	0.3657		2	1	0.4	-14.03
c.1211C>G	A404G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A404G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are premPS and SIFT. FoldX, Rosetta, and Foldetta give uncertain or inconclusive results and are treated as unavailable. The high‑accuracy consensus (SGM‑Consensus) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, remains uncertain. Overall, the majority of evidence points to a benign impact for A404G, and this assessment does not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.232838	Structured	0.415505	Uncertain	0.965	0.355	0.000											-5.277	Likely Benign	0.137	Likely Benign	Likely Benign	0.92	Ambiguous	0.0	1.88	Ambiguous	1.40	Ambiguous	1.18	Destabilizing	0.099	Likely Benign	-2.34	Neutral	0.045	Benign	0.013	Benign	4.03	Benign	0.00	Affected			0.2370	0.5054		1	0	-2.2	-14.03
c.1222A>T	T408S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T408S is not reported in ClinVar and is absent from gnomAD. All available in‑silico predictors classify it as benign: SIFT, PolyPhen‑2 (HumDiv and HumVar), REVEL, PROVEAN, FoldX, Rosetta, premPS, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Benign). No tool predicts pathogenicity. High‑accuracy assessments are consistent: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) indicates benign stability. Consequently, the variant is most likely benign, and this prediction does not contradict any ClinVar status (none available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.161087	Structured	0.370935	Uncertain	0.907	0.239	0.000											-6.277	Likely Benign	0.106	Likely Benign	Likely Benign	0.10	Likely Benign	0.0	0.39	Likely Benign	0.25	Likely Benign	0.18	Likely Benign	0.044	Likely Benign	-1.48	Neutral	0.182	Benign	0.127	Benign	4.24	Benign	0.21	Tolerated			0.3256	0.4767		1	1	-0.1	-14.03
c.1231A>G	I411V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I411V is reported in ClinVar as benign (ClinVar ID 1654508.0) and is not found in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Benign). Two tools predict a pathogenic outcome: PolyPhen‑2 HumDiv and PolyPhen‑2 HumVar. Predictions that are inconclusive or unavailable are AlphaMissense‑Default, FoldX, Rosetta, premPS, and Foldetta. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta) is uncertain. Overall, the preponderance of evidence points to a benign effect for I411V, which is consistent with its ClinVar classification and does not contradict the reported status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.116183	Structured	0.339366	Uncertain	0.927	0.198	0.000					Likely Benign		1				-6.290	Likely Benign	0.385	Ambiguous	Likely Benign	0.74	Ambiguous	0.0	0.82	Ambiguous	0.78	Ambiguous	0.99	Ambiguous	0.212	Likely Benign	-0.86	Neutral	0.935	Possibly Damaging	0.858	Possibly Damaging	3.90	Benign	0.27	Tolerated	3.38	28	0.1112	0.3526		4	3	-0.3	-14.03	233.3	28.2	-0.2	0.0	-0.2	0.0						X		Potentially Benign	The sec-butyl side chain of Ile411, located in the hydrophobic space between an anti-parallel β sheet strand (res. Pro398-Ile411) and an α helix (res. Asp684-Gln702), packs against multiple residues (e.g., Met409, Arg259). In the variant simulations, the side chain of Val411 is able to favorably fill the same hydrophobic niche despite its slightly smaller size. In short, the residue swap has no apparent negative effect on the structure based on the simulations.
c.1234T>G	L412V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L412V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the remaining tools—FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, is pathogenic. No prediction or folding stability result is missing or inconclusive. Based on the preponderance of evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status (none available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.122885	Structured	0.331108	Uncertain	0.937	0.196	0.000											-11.726	Likely Pathogenic	0.962	Likely Pathogenic	Likely Pathogenic	3.65	Destabilizing	0.0	3.52	Destabilizing	3.59	Destabilizing	1.54	Destabilizing	0.231	Likely Benign	-2.76	Deleterious	0.995	Probably Damaging	0.970	Probably Damaging	3.25	Benign	0.01	Affected			0.1275	0.3378		2	1	0.4	-14.03
c.1245G>C	E415D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E415D missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Rosetta, Foldetta, premPS, and FATHMM. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. Predictions that are inconclusive or uncertain are FoldX, ESM1b, and AlphaMissense‑Optimized. High‑accuracy assessments show that the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts pathogenicity, while Foldetta predicts a benign effect. Overall, the balance of evidence leans toward a pathogenic impact, and this conclusion does not contradict the ClinVar status, which currently contains no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.100716	Structured	0.330366	Uncertain	0.915	0.236	0.000											-7.766	In-Between	0.952	Likely Pathogenic	Ambiguous	0.75	Ambiguous	0.1	0.21	Likely Benign	0.48	Likely Benign	0.49	Likely Benign	0.220	Likely Benign	-2.60	Deleterious	0.995	Probably Damaging	0.960	Probably Damaging	3.22	Benign	0.04	Affected			0.1777	0.2075		3	2	0.0	-14.03
c.1245G>T	E415D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E415D missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Rosetta, Foldetta, premPS, and FATHMM. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. Predictions that are uncertain or inconclusive are FoldX, ESM1b, and AlphaMissense‑Optimized. High‑accuracy assessments show that AlphaMissense‑Optimized is uncertain, the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic, and Foldetta indicates a benign effect. Overall, the majority of standard tools lean toward pathogenicity, and the high‑accuracy consensus also supports a pathogenic classification. Therefore, the variant is most likely pathogenic based on current predictions, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.100716	Structured	0.330366	Uncertain	0.915	0.236	0.000											-7.766	In-Between	0.952	Likely Pathogenic	Ambiguous	0.75	Ambiguous	0.1	0.21	Likely Benign	0.48	Likely Benign	0.49	Likely Benign	0.220	Likely Benign	-2.60	Deleterious	0.995	Probably Damaging	0.960	Probably Damaging	3.22	Benign	0.04	Affected			0.1777	0.2075		3	2	0.0	-14.03
c.1246C>G	L416V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L416V is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, SIFT, AlphaMissense‑Default, AlphaMissense‑Optimized, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. Predictions that are inconclusive or unavailable are FoldX, Rosetta, Foldetta, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Benign, and Foldetta as uncertain. Overall, the majority of evidence points to a benign impact for the variant. This conclusion is not contradicted by any ClinVar annotation, as the variant is not present in that database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.104810	Structured	0.336105	Uncertain	0.935	0.227	0.000											-7.861	In-Between	0.310	Likely Benign	Likely Benign	1.46	Ambiguous	0.0	1.78	Ambiguous	1.62	Ambiguous	0.45	Likely Benign	0.124	Likely Benign	-1.47	Neutral	0.995	Probably Damaging	0.970	Probably Damaging	3.42	Benign	0.53	Tolerated			0.1563	0.3550		2	1	0.4	-14.03
c.1257G>C	E419D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E419D missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, PROVEAN, SIFT, and FATHMM. Tools that agree on a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. Uncertain or inconclusive predictions come from Foldetta, AlphaMissense‑Optimized, ESM1b, and Rosetta. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain (treated as unavailable), the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) resolves to benign, and Foldetta remains uncertain (unavailable). Overall, the majority of evidence points to a benign impact. This conclusion does not contradict ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.102787	Structured	0.371949	Uncertain	0.961	0.261	0.000											-7.036	In-Between	0.869	Likely Pathogenic	Ambiguous	0.17	Likely Benign	0.1	0.87	Ambiguous	0.52	Ambiguous	0.48	Likely Benign	0.170	Likely Benign	-2.40	Neutral	0.995	Probably Damaging	0.960	Probably Damaging	3.33	Benign	0.10	Tolerated			0.1966	0.4906		3	2	0.0	-14.03
c.1257G>T	E419D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E419D missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, PROVEAN, SIFT, and FATHMM. Tools that agree on a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. Uncertain or inconclusive predictions come from Foldetta, AlphaMissense‑Optimized, ESM1b, and Rosetta. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain (treated as unavailable), the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) resolves to benign, and Foldetta remains uncertain (unavailable). Overall, the majority of evidence points to a benign impact. This conclusion does not contradict ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.102787	Structured	0.371949	Uncertain	0.961	0.261	0.000											-7.036	In-Between	0.869	Likely Pathogenic	Ambiguous	0.17	Likely Benign	0.1	0.87	Ambiguous	0.52	Ambiguous	0.48	Likely Benign	0.170	Likely Benign	-2.40	Neutral	0.995	Probably Damaging	0.960	Probably Damaging	3.33	Benign	0.10	Tolerated			0.1966	0.4906		3	2	0.0	-14.03
c.1262C>G	A421G 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant A421G is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are Rosetta, premPS, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). FoldX and Foldetta give uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM Consensus as likely pathogenic, and Foldetta as uncertain. Overall, the majority of tools and the SGM Consensus favor a pathogenic interpretation, while a minority suggest benign. Because there is no ClinVar entry, the predictions do not contradict existing clinical classification. The variant is most likely pathogenic based on the collective computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.067594	Structured	0.404927	Uncertain	0.965	0.257	0.000											-9.699	Likely Pathogenic	0.757	Likely Pathogenic	Likely Benign	1.47	Ambiguous	0.1	2.13	Destabilizing	1.80	Ambiguous	1.19	Destabilizing	0.137	Likely Benign	-3.59	Deleterious	0.536	Possibly Damaging	0.176	Benign	3.41	Benign	0.05	Affected			0.1692	0.2499		1	0	-2.2	-14.03
c.1266G>C	E422D 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant E422D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, Rosetta, premPS, SIFT, and FATHMM; pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. ESM1b is uncertain. High‑accuracy assessments further refine the picture: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also favors pathogenic; whereas Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts benign. Overall, the majority of tools (six benign vs five pathogenic) lean toward a benign effect, but the two most accurate predictors and the consensus vote indicate a pathogenic tendency. Thus, the variant is most likely benign based on the broader tool set, and this assessment does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.067594	Structured	0.426709	Uncertain	0.965	0.255	0.000											-7.092	In-Between	0.969	Likely Pathogenic	Likely Pathogenic	0.39	Likely Benign	0.0	-0.03	Likely Benign	0.18	Likely Benign	0.21	Likely Benign	0.199	Likely Benign	-2.76	Deleterious	0.995	Probably Damaging	0.960	Probably Damaging	3.38	Benign	0.07	Tolerated			0.1686	0.2864		3	2	0.0	-14.03
c.1266G>T	E422D 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant E422D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, Rosetta, premPS, SIFT, and FATHMM; pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. ESM1b is uncertain. High‑accuracy assessments further refine the picture: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also favors pathogenic; whereas Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts benign. Overall, the majority of tools (six benign vs five pathogenic) lean toward a benign effect, but the two most accurate predictors and the consensus vote indicate a pathogenic tendency. Thus, the variant is most likely benign based on the broader tool set, and this assessment does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.067594	Structured	0.426709	Uncertain	0.965	0.255	0.000											-7.092	In-Between	0.969	Likely Pathogenic	Likely Pathogenic	0.39	Likely Benign	0.0	-0.03	Likely Benign	0.18	Likely Benign	0.21	Likely Benign	0.199	Likely Benign	-2.76	Deleterious	0.995	Probably Damaging	0.960	Probably Damaging	3.38	Benign	0.07	Tolerated			0.1686	0.2864		3	2	0.0	-14.03
c.1273A>T	T425S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T425S is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. Four tools (Foldetta, premPS, ESM1b, Rosetta) return uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of tools (five benign vs. four pathogenic) lean toward a benign interpretation, and this assessment does not contradict ClinVar status, which currently has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.041405	Structured	0.401218	Uncertain	0.964	0.280	0.000											-7.420	In-Between	0.676	Likely Pathogenic	Likely Benign	0.22	Likely Benign	0.1	0.77	Ambiguous	0.50	Ambiguous	0.63	Ambiguous	0.275	Likely Benign	-3.05	Deleterious	0.998	Probably Damaging	0.994	Probably Damaging	3.42	Benign	0.07	Tolerated			0.2511	0.2324		1	1	-0.1	-14.03
c.1274C>G	T425S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T425S is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. Four tools (Foldetta, premPS, ESM1b, Rosetta) return uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of tools (five benign vs. four pathogenic) lean toward a benign interpretation, and this assessment does not contradict ClinVar status, which currently has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.041405	Structured	0.401218	Uncertain	0.964	0.280	0.000											-7.420	In-Between	0.676	Likely Pathogenic	Likely Benign	0.22	Likely Benign	0.1	0.77	Ambiguous	0.50	Ambiguous	0.63	Ambiguous	0.184	Likely Benign	-3.05	Deleterious	0.998	Probably Damaging	0.994	Probably Damaging	3.42	Benign	0.07	Tolerated			0.2511	0.2324		1	1	-0.1	-14.03
c.1291C>G	L431V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 L431V missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, SIFT, FATHMM, AlphaMissense‑Optimized, and polyPhen‑2 HumVar. Those that predict a pathogenic effect are FoldX, premPS, PROVEAN, and polyPhen‑2 HumDiv. Four tools (Rosetta, Foldetta, ESM1b, AlphaMissense‑Default) give uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 1‑to‑1 split between benign and pathogenic signals, and Foldetta also yields an uncertain outcome. Overall, the balance of evidence—including the higher number of benign predictions and the benign call from the most accurate tool—suggests that the variant is most likely benign. This conclusion does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.094817	Structured	0.374755	Uncertain	0.959	0.300	0.000											-7.949	In-Between	0.505	Ambiguous	Likely Benign	2.17	Destabilizing	0.0	1.50	Ambiguous	1.84	Ambiguous	1.32	Destabilizing	0.093	Likely Benign	-2.58	Deleterious	0.861	Possibly Damaging	0.332	Benign	3.04	Benign	0.20	Tolerated			0.1377	0.3198		2	1	0.4	-14.03
c.1298C>G	A433G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A433G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that reach a consensus all indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all score the substitution as tolerated. No tool predicts pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized classifies the variant as benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Benign. The protein‑folding stability method Foldetta, which integrates FoldX‑MD and Rosetta outputs, yields an uncertain result and is therefore treated as unavailable evidence. Overall, the collective predictions strongly suggest that the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.098513	Structured	0.352258	Uncertain	0.938	0.302	0.000											-5.044	Likely Benign	0.107	Likely Benign	Likely Benign	0.59	Ambiguous	0.0	1.21	Ambiguous	0.90	Ambiguous	0.70	Ambiguous	0.038	Likely Benign	-1.54	Neutral	0.035	Benign	0.014	Benign	3.38	Benign	0.15	Tolerated			0.1629	0.2919		1	0	-2.2	-14.03
c.1303T>G	L435V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L435V has no ClinVar assertion and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, SIFT, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions arise from FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), and AlphaMissense‑Default. ESM1b is uncertain. High‑accuracy assessments further support a pathogenic bias: AlphaMissense‑Optimized predicts benign, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default (pathogenic), ESM1b (uncertain), FATHMM (benign), and PROVEAN (pathogenic)—favors pathogenicity. Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts pathogenic. With the preponderance of pathogenic calls from both general and high‑accuracy tools, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar claim exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.229226	Structured	0.333584	Uncertain	0.954	0.292	0.000											-7.134	In-Between	0.571	Likely Pathogenic	Likely Benign	2.97	Destabilizing	0.1	2.33	Destabilizing	2.65	Destabilizing	1.36	Destabilizing	0.217	Likely Benign	-2.80	Deleterious	0.995	Probably Damaging	0.970	Probably Damaging	3.23	Benign	0.06	Tolerated			0.1216	0.2628		2	1	0.4	-14.03
c.1308G>C	E436D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E436D missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools cluster into two groups: benign predictions are limited to FATHMM, while the remaining nine tools (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) all predict pathogenicity. Four tools (FoldX, Rosetta, Foldetta, premPS) give uncertain results and are treated as unavailable. High‑accuracy assessments further support a pathogenic interpretation: AlphaMissense‑Optimized is pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is also pathogenic (3 pathogenic vs. 1 benign). Foldetta’s stability prediction is uncertain. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.239899	Structured	0.321046	Uncertain	0.934	0.289	0.000											-10.355	Likely Pathogenic	0.979	Likely Pathogenic	Likely Pathogenic	0.55	Ambiguous	0.1	0.71	Ambiguous	0.63	Ambiguous	0.73	Ambiguous	0.554	Likely Pathogenic	-2.85	Deleterious	0.986	Probably Damaging	0.921	Probably Damaging	4.61	Benign	0.01	Affected			0.1938	0.3553		3	2	0.0	-14.03
c.1308G>T	E436D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E436D missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools cluster into two groups: benign predictions are limited to FATHMM, while the remaining nine tools (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) all predict pathogenicity. Four tools (FoldX, Rosetta, Foldetta, premPS) give uncertain results and are treated as unavailable. High‑accuracy assessments further support a pathogenic interpretation: AlphaMissense‑Optimized is pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is also pathogenic (3 pathogenic vs. 1 benign). Foldetta’s stability prediction is uncertain. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.239899	Structured	0.321046	Uncertain	0.934	0.289	0.000											-10.355	Likely Pathogenic	0.979	Likely Pathogenic	Likely Pathogenic	0.55	Ambiguous	0.1	0.71	Ambiguous	0.63	Ambiguous	0.73	Ambiguous	0.554	Likely Pathogenic	-2.85	Deleterious	0.986	Probably Damaging	0.921	Probably Damaging	4.61	Benign	0.01	Affected			0.1938	0.3553		3	2	0.0	-14.03
c.1313C>G	A438G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A438G is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote). Only PROVEAN predicts a pathogenic outcome. Predictions that are inconclusive or unavailable are FoldX, Rosetta, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus as Likely Benign, and Foldetta as uncertain. Overall, the majority of evidence points to a benign impact for A438G, and this conclusion is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.147574	Structured	0.290154	Uncertain	0.929	0.293	0.000											-5.790	Likely Benign	0.182	Likely Benign	Likely Benign	1.08	Ambiguous	0.1	1.78	Ambiguous	1.43	Ambiguous	0.80	Ambiguous	0.034	Likely Benign	-2.51	Deleterious	0.247	Benign	0.037	Benign	4.12	Benign	0.11	Tolerated			0.1788	0.2719		1	0	-2.2	-14.03
c.1315C>G	L439V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L439V is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote). Tools that predict a pathogenic effect are FoldX, Rosetta, Foldetta, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar; premPS is inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus as likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. Overall, the majority of predictions (8 benign vs. 5 pathogenic) favor a benign classification, and this consensus does not contradict the absence of ClinVar evidence. Thus, based on current computational predictions, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.222385	Structured	0.281542	Uncertain	0.942	0.265	0.000											-6.340	Likely Benign	0.279	Likely Benign	Likely Benign	2.34	Destabilizing	0.2	2.40	Destabilizing	2.37	Destabilizing	0.91	Ambiguous	0.121	Likely Benign	-1.13	Neutral	0.976	Probably Damaging	0.941	Probably Damaging	3.36	Benign	0.12	Tolerated			0.1272	0.2628		2	1	0.4	-14.03
c.1335G>C	E445D 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant E445D is reported in gnomAD (ID 6‑33438240‑G‑C) but has no ClinVar entry. Functional prediction tools show a split verdict: benign calls come from REVEL, Rosetta, SIFT, FATHMM, and AlphaMissense‑Optimized, while pathogenic calls arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and AlphaMissense‑Default. Uncertain results are reported by FoldX, Foldetta, and premPS. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta remains uncertain. Overall, the balance of evidence, especially the SGM Consensus, points to a pathogenic effect for E445D. This conclusion does not contradict ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.191378	Structured	0.270205	Uncertain	0.947	0.228	0.000								6-33438240-G-C	4	2.48e-6	-10.238	Likely Pathogenic	0.783	Likely Pathogenic	Likely Benign	0.81	Ambiguous	0.0	0.49	Likely Benign	0.65	Ambiguous	0.91	Ambiguous	0.136	Likely Benign	-2.86	Deleterious	0.977	Probably Damaging	0.921	Probably Damaging	3.54	Benign	0.09	Tolerated	3.38	31	0.1437	0.3526		2	3	0.0	-14.03
c.1335G>T	E445D 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant E445D is not reported in ClinVar (status: none) and is absent from gnomAD. Prediction tools that agree on benign include REVEL, Rosetta, SIFT, FATHMM, and AlphaMissense‑Optimized; those that agree on pathogenic include SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Uncertain or unavailable results come from FoldX, Foldetta, and premPS. High‑accuracy methods give a split view: AlphaMissense‑Optimized predicts benign, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts likely pathogenic, and Foldetta is uncertain. Overall, the predictions are inconclusive, with an equal number of benign and pathogenic calls. Thus, the variant is most likely benign based on the current evidence, and this assessment does not contradict the ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.191378	Structured	0.270205	Uncertain	0.947	0.228	0.000											-10.238	Likely Pathogenic	0.783	Likely Pathogenic	Likely Benign	0.81	Ambiguous	0.0	0.49	Likely Benign	0.65	Ambiguous	0.91	Ambiguous	0.136	Likely Benign	-2.86	Deleterious	0.977	Probably Damaging	0.921	Probably Damaging	3.54	Benign	0.09	Tolerated	3.38	31	0.1437	0.3526		2	3	0.0	-14.03
c.1338G>C	E446D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E446D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a damaging effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. Predictions that are inconclusive or unavailable are FoldX, Rosetta, Foldetta, premPS, and AlphaMissense‑Default. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized scores the variant as benign; the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports it as Likely Benign; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, yields an uncertain result. Taken together, the majority of evidence points to a benign impact, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.271506	Structured	0.276479	Uncertain	0.940	0.216	0.000											-5.668	Likely Benign	0.562	Ambiguous	Likely Benign	1.65	Ambiguous	0.7	0.80	Ambiguous	1.23	Ambiguous	0.68	Ambiguous	0.171	Likely Benign	-2.40	Neutral	0.986	Probably Damaging	0.960	Probably Damaging	3.30	Benign	0.18	Tolerated			0.1657	0.4275		3	2	0.0	-14.03
c.1338G>T	E446D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense change E446D lies in the GAP domain. ClinVar has no entry for this variant and it is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Two tools report a pathogenic signal: polyPhen‑2 HumDiv and polyPhen‑2 HumVar. The remaining predictors (FoldX, Rosetta, Foldetta, premPS, AlphaMissense‑Default) give uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus also benign, whereas Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is inconclusive. Taken together, the majority of evidence points to a benign effect. Thus, the variant is most likely benign, and this is consistent with the lack of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.271506	Structured	0.276479	Uncertain	0.940	0.216	0.000											-5.668	Likely Benign	0.562	Ambiguous	Likely Benign	1.65	Ambiguous	0.7	0.80	Ambiguous	1.23	Ambiguous	0.68	Ambiguous	0.171	Likely Benign	-2.40	Neutral	0.986	Probably Damaging	0.960	Probably Damaging	3.30	Benign	0.18	Tolerated			0.1657	0.4275		3	2	0.0	-14.03
c.1343C>G	A448G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A448G resides in the GAP domain. ClinVar has no entry for this variant, and it is not reported in gnomAD. Prediction tools that classify it as benign include REVEL, SIFT, FATHMM, and AlphaMissense‑Optimized, whereas those that predict pathogenicity are Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and AlphaMissense‑Default; FoldX is inconclusive. High‑accuracy assessments further clarify the impact: AlphaMissense‑Optimized reports a benign effect, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates pathogenicity, and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts a pathogenic effect. Based on the preponderance of pathogenic predictions and the high‑accuracy consensus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.225814	Structured	0.292774	Uncertain	0.973	0.257	0.000											-9.984	Likely Pathogenic	0.640	Likely Pathogenic	Likely Benign	1.76	Ambiguous	0.0	2.45	Destabilizing	2.11	Destabilizing	1.00	Destabilizing	0.378	Likely Benign	-3.95	Deleterious	0.998	Probably Damaging	0.980	Probably Damaging	3.15	Benign	0.06	Tolerated			0.2135	0.2936		1	0	-2.2	-14.03
c.1349C>G	A450G 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant A450G is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized. The majority of other in silico predictors (SGM‑Consensus, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) classify the variant as pathogenic; FoldX is inconclusive. High‑accuracy assessments further support a pathogenic interpretation: AlphaMissense‑Optimized predicts benign, but the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) and Foldetta (combining FoldX‑MD and Rosetta) both predict pathogenic. Overall, the preponderance of evidence indicates that A450G is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.321458	Structured	0.306281	Uncertain	0.963	0.234	0.000											-11.090	Likely Pathogenic	0.695	Likely Pathogenic	Likely Benign	1.79	Ambiguous	0.0	2.29	Destabilizing	2.04	Destabilizing	1.23	Destabilizing	0.355	Likely Benign	-3.82	Deleterious	0.998	Probably Damaging	0.980	Probably Damaging	3.40	Benign	0.04	Affected			0.1670	0.3078		1	0	-2.2	-14.03
c.1351C>G	L451V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L451V is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized. In contrast, the majority of tools predict a pathogenic impact: SGM‑Consensus (Likely Pathogenic), FoldX, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Rosetta is uncertain and does not contribute to the consensus. High‑accuracy methods give the following results: AlphaMissense‑Optimized predicts benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts likely pathogenic; and Foldetta predicts pathogenic. Overall, the preponderance of evidence points to a pathogenic effect for L451V. This conclusion is not contradicted by ClinVar, which has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.281712	Structured	0.314017	Uncertain	0.978	0.232	0.000											-10.732	Likely Pathogenic	0.635	Likely Pathogenic	Likely Benign	2.83	Destabilizing	0.1	1.81	Ambiguous	2.32	Destabilizing	1.39	Destabilizing	0.325	Likely Benign	-2.90	Deleterious	0.995	Probably Damaging	0.970	Probably Damaging	2.54	Benign	0.01	Affected			0.1065	0.2856		2	1	0.4	-14.03
c.1360A>G	I454V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I454V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. Predictions that are inconclusive or unavailable are FoldX, Rosetta, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus as likely benign, and Foldetta as uncertain. Based on the collective evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.254060	Structured	0.312811	Uncertain	0.965	0.182	0.000											-4.719	Likely Benign	0.657	Likely Pathogenic	Likely Benign	1.47	Ambiguous	0.0	1.36	Ambiguous	1.42	Ambiguous	0.69	Ambiguous	0.132	Likely Benign	-0.79	Neutral	0.935	Possibly Damaging	0.858	Possibly Damaging	3.40	Benign	0.18	Tolerated			0.0833	0.2959		4	3	-0.3	-14.03
c.1363C>G	L455V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L455V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: benign predictions come from REVEL and FATHMM, whereas the remaining 11 tools (FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) predict pathogenicity. High‑accuracy assessments reinforce this trend: AlphaMissense‑Optimized is uncertain; the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts pathogenicity. Taken together, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion is consistent with the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.188120	Structured	0.310377	Uncertain	0.963	0.168	0.000											-12.773	Likely Pathogenic	0.946	Likely Pathogenic	Ambiguous	2.89	Destabilizing	0.1	2.38	Destabilizing	2.64	Destabilizing	1.41	Destabilizing	0.276	Likely Benign	-2.83	Deleterious	0.995	Probably Damaging	0.970	Probably Damaging	3.29	Benign	0.02	Affected			0.1149	0.3056		2	1	0.4	-14.03
c.1372A>T	T458S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 T458S missense variant has no ClinVar entry and is not present in gnomAD. Functional prediction tools cluster into two groups: benign calls from REVEL, FoldX, Rosetta, SIFT, and FATHMM; pathogenic calls from SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Two tools report uncertainty: premPS and AlphaMissense‑Optimized. High‑accuracy assessments further split the signal: AlphaMissense‑Optimized remains uncertain, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts likely pathogenic, while Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign. Because the majority of standard predictors are evenly divided and the high‑accuracy methods disagree, the variant’s effect cannot be confidently classified as benign or pathogenic. Thus, the variant is of uncertain significance, and this uncertainty does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.185198	Structured	0.294848	Uncertain	0.915	0.144	0.000											-8.465	Likely Pathogenic	0.915	Likely Pathogenic	Ambiguous	0.44	Likely Benign	0.1	0.35	Likely Benign	0.40	Likely Benign	0.55	Ambiguous	0.260	Likely Benign	-3.49	Deleterious	0.998	Probably Damaging	0.994	Probably Damaging	3.48	Benign	0.13	Tolerated			0.3525	0.4349		1	1	-0.1	-14.03
c.1382C>G	A461G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A461G has no ClinVar entry and is not reported in gnomAD. Prediction tools cluster into three groups: benign predictions come from REVEL, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions arise from Rosetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b; the remaining tools (FoldX, premPS, AlphaMissense‑Default, Foldetta) give uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of evidence points toward a pathogenic effect, with no ClinVar record to contradict this assessment. Thus, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.179055	Structured	0.292531	Uncertain	0.936	0.151	0.125											-11.360	Likely Pathogenic	0.556	Ambiguous	Likely Benign	1.46	Ambiguous	0.1	2.06	Destabilizing	1.76	Ambiguous	0.83	Ambiguous	0.276	Likely Benign	-3.79	Deleterious	0.991	Probably Damaging	0.628	Possibly Damaging	3.32	Benign	0.00	Affected			0.1988	0.3317		1	0	-2.2	-14.03
c.1393C>G	L465V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L465V is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL and SIFT, while the remaining tools—FoldX, Rosetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default—indicate pathogenicity. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is uncertain; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports likely pathogenic; and Foldetta, which combines FoldX‑MD and Rosetta stability outputs, predicts pathogenic. Overall, the majority of evidence points to a pathogenic impact, which is consistent with the ClinVar uncertain status and does not contradict it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.346032	Structured	0.319240	Uncertain	0.956	0.202	0.000					Uncertain		1				-9.893	Likely Pathogenic	0.838	Likely Pathogenic	Ambiguous	2.46	Destabilizing	0.1	2.66	Destabilizing	2.56	Destabilizing	1.21	Destabilizing	0.276	Likely Benign	-2.98	Deleterious	0.996	Probably Damaging	0.992	Probably Damaging	2.44	Pathogenic	0.10	Tolerated	3.37	34	0.1493	0.3378		2	1	0.4	-14.03	204.3	30.9	0.0	0.0	-0.4	0.6						X		Potentially Benign	The iso-butyl side chain of Leu465, located in the middle of an α helix (res. Ala461–Phe476), packs with hydrophobic residues (e.g., Phe464, Met468, Tyr497, Ile494) in an inter-helix space formed with two other α helices (res. Ala461–Phe476 and res. Thr488-Gly502). In the variant simulations, the iso-propyl side chain of Val465 is equally sized and similarly hydrophobic as the original side chain of Leu465. Hence, the mutation does not exert any negative effects on the protein structure based on the variant simulations.
c.1406C>G	A469G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A469G is not reported in ClinVar (ClinVar status: not listed) and is absent from gnomAD. Prediction tools that agree on a benign effect include PROVEAN, SIFT, ESM1b, and AlphaMissense‑Optimized. Those that predict a pathogenic effect comprise REVEL, Rosetta, Foldetta, premPS, polyPhen‑2 (HumDiv and HumVar), FATHMM, and AlphaMissense‑Default; FoldX is uncertain. High‑accuracy methods give mixed results: AlphaMissense‑Optimized indicates benign, Foldetta indicates pathogenic, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑to‑2 split. Overall, the majority of tools (12 vs. 4) predict pathogenicity, and there is no ClinVar entry to contradict this assessment. Thus, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.278302	Structured	0.343926	Uncertain	0.910	0.276	0.000											-4.438	Likely Benign	0.733	Likely Pathogenic	Likely Benign	1.99	Ambiguous	0.1	2.22	Destabilizing	2.11	Destabilizing	1.01	Destabilizing	0.569	Likely Pathogenic	-2.42	Neutral	0.997	Probably Damaging	0.990	Probably Damaging	-1.32	Pathogenic	0.37	Tolerated			0.1797	0.3078		1	0	-2.2	-14.03
c.1416G>C	E472D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E472D is not reported in ClinVar and has no gnomAD entry. Consensus from multiple in‑silico predictors shows a split: benign calls come from REVEL and SIFT, whereas the majority of tools—SGM‑Consensus, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict pathogenicity. FoldX, Rosetta, and Foldetta provide uncertain or inconclusive stability estimates. High‑accuracy methods reinforce the pathogenic signal: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (derived from the four high‑confidence predictors) is pathogenic, and Foldetta remains uncertain. Overall, the preponderance of evidence points to a pathogenic effect for E472D, and this assessment does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.264545	Structured	0.359300	Uncertain	0.878	0.231	0.000											-9.798	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	1.27	Ambiguous	0.3	1.99	Ambiguous	1.63	Ambiguous	1.00	Destabilizing	0.304	Likely Benign	-2.75	Deleterious	0.989	Probably Damaging	0.979	Probably Damaging	2.43	Pathogenic	0.06	Tolerated			0.1975	0.3918		3	2	0.0	-14.03
c.1416G>T	E472D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E472D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL and SIFT, whereas a majority of tools predict a pathogenic impact: polyPhen‑2 (HumDiv and HumVar), FATHMM, ESM1b, PROVEAN, AlphaMissense‑Default, AlphaMissense‑Optimized, premPS, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Stability‑based methods (FoldX, Rosetta, Foldetta) yield uncertain results and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus as Likely Pathogenic, and Foldetta as uncertain. Overall, the preponderance of evidence from multiple independent predictors indicates that the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.264545	Structured	0.359300	Uncertain	0.878	0.231	0.000											-9.798	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	1.27	Ambiguous	0.3	1.99	Ambiguous	1.63	Ambiguous	1.00	Destabilizing	0.303	Likely Benign	-2.75	Deleterious	0.989	Probably Damaging	0.979	Probably Damaging	2.43	Pathogenic	0.06	Tolerated			0.1975	0.3918		3	2	0.0	-14.03
c.1434A>C	E478D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E478D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). No tool predicts a pathogenic outcome; the only inconclusive result is from Rosetta, which is treated as unavailable. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, SGM‑Consensus (majority vote) indicates likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign. Based on the collective evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.264545	Structured	0.414660	Uncertain	0.787	0.249	0.000											-1.004	Likely Benign	0.085	Likely Benign	Likely Benign	-0.04	Likely Benign	0.0	-0.65	Ambiguous	-0.35	Likely Benign	-0.28	Likely Benign	0.175	Likely Benign	0.55	Neutral	0.000	Benign	0.001	Benign	3.53	Benign	0.70	Tolerated			0.1768	0.3315		3	2	0.0	-14.03
c.1434A>T	E478D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E478D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). No tool predicts a pathogenic outcome; the only inconclusive result is from Rosetta, which is treated as unavailable. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, SGM‑Consensus is “Likely Benign,” and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign. Based on the collective evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.264545	Structured	0.414660	Uncertain	0.787	0.249	0.000											-1.004	Likely Benign	0.085	Likely Benign	Likely Benign	-0.04	Likely Benign	0.0	-0.65	Ambiguous	-0.35	Likely Benign	-0.28	Likely Benign	0.175	Likely Benign	0.55	Neutral	0.000	Benign	0.001	Benign	3.53	Benign	0.70	Tolerated			0.1768	0.3315		3	2	0.0	-14.03
c.1440G>C	E480D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E480D missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, and ESM1b, whereas polyPhen‑2 (HumDiv and HumVar) and FATHMM predict a pathogenic impact. The remaining tools—FoldX, Rosetta, premPS, AlphaMissense‑Default, and Foldetta—return uncertain or inconclusive results and are treated as unavailable evidence. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a benign majority, and Foldetta remains uncertain. Overall, the balance of evidence favors a benign classification for E480D, and this conclusion does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.216401	Structured	0.426867	Uncertain	0.798	0.250	0.000											-3.001	Likely Benign	0.475	Ambiguous	Likely Benign	0.62	Ambiguous	0.2	1.39	Ambiguous	1.01	Ambiguous	0.61	Ambiguous	0.405	Likely Benign	-0.77	Neutral	0.989	Probably Damaging	0.979	Probably Damaging	-1.27	Pathogenic	0.28	Tolerated			0.1526	0.4130		3	2	0.0	-14.03
c.1440G>T	E480D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E480D missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, and ESM1b, while polyPhen‑2 (HumDiv and HumVar) and FATHMM predict a pathogenic outcome. The remaining tools—FoldX, Rosetta, premPS, AlphaMissense‑Default, and Foldetta—return uncertain or inconclusive results and are treated as unavailable evidence. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) leaning toward benign, and Foldetta providing no definitive stability change. Overall, the balance of evidence favors a benign interpretation, and this conclusion does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.216401	Structured	0.426867	Uncertain	0.798	0.250	0.000											-3.001	Likely Benign	0.475	Ambiguous	Likely Benign	0.62	Ambiguous	0.2	1.39	Ambiguous	1.01	Ambiguous	0.61	Ambiguous	0.405	Likely Benign	-0.77	Neutral	0.989	Probably Damaging	0.979	Probably Damaging	-1.27	Pathogenic	0.28	Tolerated			0.1526	0.4130		3	2	0.0	-14.03
c.1444C>G	L482V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L482V has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include SIFT and AlphaMissense‑Optimized, whereas a majority of tools (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default) predict a pathogenic impact. Stability‑based methods (FoldX, Rosetta, Foldetta, premPS) are inconclusive and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—indicates pathogenicity; Foldetta remains uncertain. Overall, the preponderance of evidence points to a pathogenic effect for the variant, and this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.254060	Structured	0.426236	Uncertain	0.795	0.248	0.000											-11.676	Likely Pathogenic	0.734	Likely Pathogenic	Likely Benign	1.97	Ambiguous	0.1	1.52	Ambiguous	1.75	Ambiguous	0.76	Ambiguous	0.709	Likely Pathogenic	-2.95	Deleterious	0.989	Probably Damaging	0.984	Probably Damaging	-1.30	Pathogenic	0.10	Tolerated			0.1074	0.2027		2	1	0.4	-14.03
c.1447A>G	I483V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I483V is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Functional prediction tools show mixed results: benign predictions come from REVEL, Rosetta, PROVEAN, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions are reported by premPS, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b. Predictions marked as uncertain include FoldX, Foldetta, and AlphaMissense‑Default. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields benign, whereas Foldetta remains uncertain. Overall, the balance of evidence from both general and high‑accuracy tools leans toward a benign effect, which does not contradict the ClinVar designation of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.206376	Structured	0.415850	Uncertain	0.798	0.254	0.000					Conflicting		2				-10.121	Likely Pathogenic	0.523	Ambiguous	Likely Benign	1.00	Ambiguous	0.0	0.27	Likely Benign	0.64	Ambiguous	1.02	Destabilizing	0.228	Likely Benign	-0.86	Neutral	0.914	Possibly Damaging	0.921	Probably Damaging	3.23	Benign	0.03	Affected	3.37	32	0.0876	0.2691		3	4	-0.3	-14.03
c.1458G>C	E486D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E486D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign calls (REVEL, FoldX, Rosetta, SIFT, FATHMM) and pathogenic calls (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default). Two tools are uncertain (premPS, AlphaMissense‑Optimized). High‑accuracy assessments give mixed results: AlphaMissense‑Optimized is inconclusive; the SGM‑Consensus majority vote (AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts likely pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts benign. Because the majority of standard predictors lean toward pathogenic and the SGM‑Consensus also indicates pathogenic, the variant is most likely pathogenic, although the Foldetta benign prediction and the presence of uncertain calls leave room for ambiguity. This assessment does not contradict ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.196879	Structured	0.358545	Uncertain	0.833	0.245	0.125											-10.363	Likely Pathogenic	0.914	Likely Pathogenic	Ambiguous	0.19	Likely Benign	0.0	0.38	Likely Benign	0.29	Likely Benign	0.54	Ambiguous	0.166	Likely Benign	-2.58	Deleterious	0.994	Probably Damaging	0.979	Probably Damaging	3.43	Benign	0.16	Tolerated			0.1453	0.4115		3	2	0.0	-14.03
c.1458G>T	E486D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E486D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign calls (REVEL, FoldX, Rosetta, SIFT, FATHMM) and pathogenic calls (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default). Two tools are uncertain (premPS, AlphaMissense‑Optimized). High‑accuracy assessments give mixed results: AlphaMissense‑Optimized is inconclusive; the SGM‑Consensus majority vote (AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts likely pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts benign. Because the majority of standard predictors lean toward pathogenic and the SGM‑Consensus also indicates pathogenic, the variant is most likely pathogenic, although the Foldetta benign prediction and the presence of uncertain calls leave room for ambiguity. This assessment does not contradict ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.196879	Structured	0.358545	Uncertain	0.833	0.245	0.125											-10.363	Likely Pathogenic	0.914	Likely Pathogenic	Ambiguous	0.19	Likely Benign	0.0	0.38	Likely Benign	0.29	Likely Benign	0.54	Ambiguous	0.166	Likely Benign	-2.58	Deleterious	0.994	Probably Damaging	0.979	Probably Damaging	3.43	Benign	0.16	Tolerated			0.1453	0.4115		3	2	0.0	-14.03
c.1462A>T	T488S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 T488S missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. Four tools (Foldetta, premPS, ESM1b, and Rosetta) return uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of standard tools lean toward a benign interpretation, but the high‑accuracy consensus is split, leaving the variant’s impact ambiguous. No ClinVar annotation contradicts these predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.206376	Structured	0.332663	Uncertain	0.928	0.233	0.125											-7.662	In-Between	0.745	Likely Pathogenic	Likely Benign	0.35	Likely Benign	0.1	0.90	Ambiguous	0.63	Ambiguous	0.77	Ambiguous	0.257	Likely Benign	-3.51	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	3.73	Benign	0.31	Tolerated			0.2256	0.2813		1	1	-0.1	-14.03
c.1465C>G	L489V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L489V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: pathogenic calls come from SGM‑Consensus, REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM, while only AlphaMissense‑Optimized predicts a benign outcome. Uncertain results are reported by Rosetta, Foldetta, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as inconclusive. Overall, the preponderance of evidence points to a pathogenic effect for L489V. This conclusion is consistent with the lack of ClinVar annotation and does not contradict any existing database record. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.191378	Structured	0.326126	Uncertain	0.949	0.234	0.125											-9.345	Likely Pathogenic	0.467	Ambiguous	Likely Benign	2.09	Destabilizing	0.0	1.70	Ambiguous	1.90	Ambiguous	1.25	Destabilizing	0.586	Likely Pathogenic	-2.55	Deleterious	0.998	Probably Damaging	0.992	Probably Damaging	-1.34	Pathogenic	0.01	Affected			0.1665	0.4108		2	1	0.4	-14.03
c.1469C>G	A490G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A490G is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only AlphaMissense‑Optimized. Those that predict a pathogenic effect comprise REVEL, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and the SGM‑Consensus (Likely Pathogenic). Predictions that are uncertain or inconclusive are FoldX, Foldetta, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of evidence points to a pathogenic impact for A490G. This conclusion does not contradict ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.120615	Structured	0.322979	Uncertain	0.938	0.210	0.125											-9.767	Likely Pathogenic	0.384	Ambiguous	Likely Benign	1.24	Ambiguous	0.0	2.00	Destabilizing	1.62	Ambiguous	1.13	Destabilizing	0.744	Likely Pathogenic	-3.44	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	-1.46	Pathogenic	0.01	Affected			0.2051	0.2228		1	0	-2.2	-14.03
c.1471A>T	T491S 2D AIThe SynGAP1 missense variant T491S is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include only SIFT, whereas the majority of tools predict a pathogenic impact: REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (which is a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta as uncertain. No evidence from FoldX or Rosetta is available to support a stability change. Overall, the preponderance of evidence points to a pathogenic effect for T491S, and this conclusion does not contradict any ClinVar annotation because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.064632	Structured	0.325158	Uncertain	0.929	0.188	0.125											-7.273	In-Between	0.924	Likely Pathogenic	Ambiguous	0.93	Ambiguous	0.7	1.27	Ambiguous	1.10	Ambiguous	1.00	Destabilizing	0.704	Likely Pathogenic	-3.90	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	-1.25	Pathogenic	0.19	Tolerated			0.3119	0.2815		1	1	-0.1	-14.03
c.1472C>G	T491S 2D AIThe SynGAP1 missense variant T491S is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include only SIFT, whereas the majority of tools predict a pathogenic impact: REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (which is a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta as uncertain. No evidence from FoldX or Rosetta is available to support a stability change. Overall, the preponderance of evidence points to a pathogenic effect for T491S, and this conclusion does not contradict any ClinVar annotation because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.064632	Structured	0.325158	Uncertain	0.929	0.188	0.125											-7.273	In-Between	0.924	Likely Pathogenic	Ambiguous	0.93	Ambiguous	0.7	1.27	Ambiguous	1.10	Ambiguous	1.00	Destabilizing	0.666	Likely Pathogenic	-3.90	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	-1.25	Pathogenic	0.19	Tolerated			0.3119	0.2815		1	1	-0.1	-14.03
c.1478C>G	A493G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A493G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus all predict pathogenicity, while only AlphaMissense‑Optimized predicts a benign outcome. Predictions from FoldX, Rosetta, and Foldetta are uncertain and therefore not considered evidence. High‑accuracy assessments show AlphaMissense‑Optimized as benign, whereas the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) remains pathogenic; Foldetta likewise yields an uncertain result. Overall, the preponderance of evidence points to a pathogenic effect for A493G, and this conclusion does not contradict the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.102787	Structured	0.340081	Uncertain	0.966	0.182	0.000											-11.379	Likely Pathogenic	0.571	Likely Pathogenic	Likely Benign	1.85	Ambiguous	0.0	1.63	Ambiguous	1.74	Ambiguous	1.40	Destabilizing	0.764	Likely Pathogenic	-3.54	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	-1.40	Pathogenic	0.02	Affected			0.1673	0.2228		1	0	-2.2	-14.03
c.1480A>G	I494V 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant I494V is listed in ClinVar with an uncertain significance and is present in gnomAD (ID 6‑33438512‑A‑G). Functional prediction tools that agree on benign impact include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. Pathogenic predictions come from premPS and FATHMM. Predictions that are inconclusive are FoldX, Rosetta, Foldetta, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields benign; Foldetta remains uncertain. Overall, the majority of evidence supports a benign effect, which does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.155435	Structured	0.353330	Uncertain	0.941	0.157	0.000					Conflicting		2	6-33438512-A-G	36	2.23e-5	-7.102	In-Between	0.112	Likely Benign	Likely Benign	1.16	Ambiguous	0.0	0.71	Ambiguous	0.94	Ambiguous	1.02	Destabilizing	0.439	Likely Benign	-0.83	Neutral	0.278	Benign	0.179	Benign	-1.30	Pathogenic	0.07	Tolerated	3.37	35	0.0965	0.2491		4	3	-0.3	-14.03	248.6	29.3	0.0	0.0	-1.1	0.5						X		Potentially Benign	The sec-butyl side chain of Ile494, located in an α-helix (res. Leu489-Glu519), packs against hydrophobic residues (e.g., Phe484, Leu465, Trp572, Ala493, Met468) in an inter-helix space (res. Leu489-Glu519 and res. Ala461-Phe476). In the variant simulations, the hydrophobic iso-propyl side chain of Val494, which is of a similar size and has similar physicochemical properties to Ile494 in the WT, resides similarly in the inter-helix hydrophobic space. Thus, no negative effects on the protein structure are observed.
c.1485A>C	E495D 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant E495D is listed in ClinVar with an uncertain significance (ClinVar ID 2000233.0) and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions from SIFT and ESM1b, and pathogenic predictions from REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy consensus (SGM Consensus) derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN classifies the variant as likely pathogenic. AlphaMissense‑Optimized also predicts pathogenicity, whereas Foldetta, which integrates FoldX‑MD and Rosetta outputs, remains uncertain. Overall, the majority of evidence points to a pathogenic effect, which does not contradict the ClinVar uncertain status but suggests a higher likelihood of deleterious impact. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.164327	Structured	0.364496	Uncertain	0.933	0.161	0.000					Conflicting		2				-3.574	Likely Benign	0.958	Likely Pathogenic	Likely Pathogenic	1.39	Ambiguous	0.1	1.03	Ambiguous	1.21	Ambiguous	0.98	Ambiguous	0.566	Likely Pathogenic	-2.52	Deleterious	0.998	Probably Damaging	0.989	Probably Damaging	-1.41	Pathogenic	0.17	Tolerated	3.37	35	0.1778	0.3064		3	2	0.0	-14.03	220.6	38.8	0.0	0.0	0.1	0.1		X		X				Uncertain	Glu495 is located in the α-helix (res. Leu489-Glu519), and its carboxylate group forms salt bridges with the neighboring Lys492 and with Arg596 on an opposing α-helix (res. Glu582-Met603) in the WT simulations. In the variant simulations, the acidic carboxylate side chain of Asp495 can also form salt bridges with both Lys492 and Arg596. However, the shorter side chain of aspartate tends to favor forming a salt bridge with the nearby Arg499 on the same α-helix instead. Asp495 might not maintain the salt bridge with Arg596 on the opposing α-helix as efficiently as Glu495 in the WT, potentially weakening the tertiary structure. Regardless, the potential negative effect is likely to be minor, with no deleterious effects observed on the protein structure during the simulations. However, due to its location at the GAP-Ras interface, the effect of the residue swap on SynGAP-Ras complex formation or GTPase activation cannot be fully addressed using the SynGAP solvent-only simulations.
c.1485A>T	E495D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E495D is not reported in ClinVar (status: None) and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from SIFT and ESM1b, while pathogenic predictions arise from REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus. Four tools (FoldX, Rosetta, Foldetta, premPS) give uncertain or inconclusive results and are treated as unavailable. High‑accuracy methods reinforce the pathogenic signal: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts pathogenic, and Foldetta provides no definitive stability change. Overall, the variant is most likely pathogenic based on the consensus of predictive algorithms, and this assessment does not contradict any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.164327	Structured	0.364496	Uncertain	0.933	0.161	0.000											-3.574	Likely Benign	0.958	Likely Pathogenic	Likely Pathogenic	1.39	Ambiguous	0.1	1.03	Ambiguous	1.21	Ambiguous	0.98	Ambiguous	0.566	Likely Pathogenic	-2.52	Deleterious	0.998	Probably Damaging	0.989	Probably Damaging	-1.41	Pathogenic	0.17	Tolerated	3.37	35	0.1778	0.3064		3	2	0.0	-14.03	220.6	38.8	0.0	0.0	0.1	0.1		X		X				Uncertain	Glu495 is located in the α-helix (res. Leu489-Glu519), and its carboxylate group forms salt bridges with the neighboring Lys492 and with Arg596 on an opposing α-helix (res. Glu582-Met603) in the WT simulations. In the variant simulations, the acidic carboxylate side chain of Asp495 can also form salt bridges with both Lys492 and Arg596. However, the shorter side chain of aspartate tends to favor forming a salt bridge with the nearby Arg499 on the same α-helix instead. Asp495 might not maintain the salt bridge with Arg596 on the opposing α-helix as efficiently as Glu495 in the WT, potentially weakening the tertiary structure. Regardless, the potential negative effect is likely to be minor, with no deleterious effects observed on the protein structure during the simulations. However, due to its location at the GAP-Ras interface, the effect of the residue swap on SynGAP-Ras complex formation or GTPase activation cannot be fully addressed using the SynGAP solvent-only simulations.
c.1488G>C	E496D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E496D missense variant is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only FoldX, whereas the majority of tools predict a pathogenic impact: SGM‑Consensus, REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Uncertain predictions come from Rosetta, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (derived from a unanimous majority of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the preponderance of evidence points to a pathogenic effect. This conclusion is consistent with the absence of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.102787	Structured	0.383296	Uncertain	0.945	0.179	0.000											-10.552	Likely Pathogenic	0.922	Likely Pathogenic	Ambiguous	0.43	Likely Benign	0.2	1.78	Ambiguous	1.11	Ambiguous	1.18	Destabilizing	0.583	Likely Pathogenic	-2.78	Deleterious	0.996	Probably Damaging	0.989	Probably Damaging	-1.45	Pathogenic	0.04	Affected	3.37	35	0.1576	0.1912		2	3	0.0	-14.03
c.1488G>T	E496D 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant E496D is reported in gnomAD (ID 6‑33438520‑G‑T) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions are provided only by FoldX, whereas the remaining tools—REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus—classify the change as pathogenic. Uncertain results come from Rosetta, Foldetta, and AlphaMissense‑Optimized and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the preponderance of evidence points to a pathogenic effect, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.102787	Structured	0.383296	Uncertain	0.945	0.179	0.000								6-33438520-G-T	2	1.24e-6	-10.552	Likely Pathogenic	0.922	Likely Pathogenic	Ambiguous	0.43	Likely Benign	0.2	1.78	Ambiguous	1.11	Ambiguous	1.18	Destabilizing	0.583	Likely Pathogenic	-2.78	Deleterious	0.996	Probably Damaging	0.989	Probably Damaging	-1.45	Pathogenic	0.04	Affected	3.37	35	0.1576	0.1912		2	3	0.0	-14.03
c.148A>G	I50V 2D AIThe SynGAP1 missense variant I50V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The high‑accuracy consensus methods also support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence indicates that I50V is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.295083	Structured	0.449965	Uncertain	0.545	0.708	0.000											-1.051	Likely Benign	0.141	Likely Benign	Likely Benign										0.082	Likely Benign	-0.24	Neutral	0.000	Benign	0.001	Benign	4.18	Benign	0.00	Affected			0.1091	0.3159		4	3	-0.3	-14.03
c.1498C>G	L500V 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L500V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on benign effect include SIFT and AlphaMissense‑Optimized, whereas a majority of tools predict pathogenicity: SGM‑Consensus, REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. Predictions that are inconclusive are FoldX, Rosetta, Foldetta, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the preponderance of evidence from multiple independent predictors indicates that the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.066181	Structured	0.382942	Uncertain	0.893	0.150	0.000											-12.963	Likely Pathogenic	0.379	Ambiguous	Likely Benign	1.92	Ambiguous	0.0	0.81	Ambiguous	1.37	Ambiguous	1.11	Destabilizing	0.565	Likely Pathogenic	-2.98	Deleterious	0.998	Probably Damaging	0.992	Probably Damaging	-1.24	Pathogenic	0.11	Tolerated			0.1205	0.1860		2	1	0.4	-14.03
c.1501A>G	I501V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I501V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. Predictions from FoldX, Rosetta, and Foldetta are uncertain and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus as likely benign, and Foldetta as uncertain. Overall, the majority of evidence points to a benign impact for I501V, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.079919	Structured	0.366596	Uncertain	0.886	0.153	0.000											-2.326	Likely Benign	0.083	Likely Benign	Likely Benign	0.94	Ambiguous	0.0	0.56	Ambiguous	0.75	Ambiguous	0.06	Likely Benign	0.200	Likely Benign	0.20	Neutral	0.951	Possibly Damaging	0.960	Probably Damaging	3.52	Benign	1.00	Tolerated			0.0985	0.2491		4	3	-0.3	-14.03
c.1516C>G	L506V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L506V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL and AlphaMissense‑Optimized, whereas the majority of other in silico predictors (FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and the SGM Consensus) all indicate a pathogenic impact. AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized predicts a benign outcome, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. Based on the preponderance of pathogenic predictions and the high‑accuracy tools’ results, the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.034884	Structured	0.279180	Uncertain	0.924	0.196	0.000											-10.220	Likely Pathogenic	0.512	Ambiguous	Likely Benign	2.61	Destabilizing	0.2	3.27	Destabilizing	2.94	Destabilizing	1.36	Destabilizing	0.420	Likely Benign	-2.98	Deleterious	0.996	Probably Damaging	0.992	Probably Damaging	1.62	Pathogenic	0.04	Affected			0.1126	0.1660		2	1	0.4	-14.03
c.151A>G	I51V 2D AIThe SynGAP1 missense variant I51V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign effect. The variant is most likely benign, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.291804	Structured	0.454181	Uncertain	0.606	0.710	0.000											-3.397	Likely Benign	0.195	Likely Benign	Likely Benign										0.065	Likely Benign	-0.24	Neutral	0.004	Benign	0.007	Benign	4.26	Benign	0.00	Affected			0.1330	0.3602		4	3	-0.3	-14.03
c.1526C>G	A509G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A509G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that clearly indicate benign effect include only AlphaMissense‑Optimized. All other evaluated tools that provide a definitive call predict pathogenicity: SGM‑Consensus, REVEL, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM. Tools with inconclusive results (AlphaMissense‑Default, FoldX, and Foldetta) are treated as unavailable and do not influence the overall assessment. High‑accuracy methods give the following: AlphaMissense‑Optimized predicts benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic; Foldetta, combining FoldX‑MD (uncertain) and Rosetta (pathogenic), is uncertain. Overall, the majority of definitive predictions support a pathogenic effect. Thus, the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.025762	Structured	0.250110	Uncertain	0.923	0.256	0.000											-11.873	Likely Pathogenic	0.541	Ambiguous	Likely Benign	1.36	Ambiguous	0.2	2.33	Destabilizing	1.85	Ambiguous	1.14	Destabilizing	0.804	Likely Pathogenic	-3.57	Deleterious	0.911	Possibly Damaging	0.706	Possibly Damaging	-1.39	Pathogenic	0.00	Affected			0.2193	0.4213		1	0	-2.2	-14.03
c.1528A>G	I510V 2D 3DClick to see structure in 3D Viewer AISynGAP1 I510V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Benign). Pathogenic predictions arise from polyPhen‑2 HumDiv, SIFT, FATHMM, and premPS. FoldX and Rosetta analyses are inconclusive, and Foldetta stability assessment is unavailable. High‑accuracy methods reinforce the benign trend: AlphaMissense‑Optimized predicts benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also favors benign, while Foldetta provides no definitive result. Overall, the majority of evidence points to a benign effect for I510V, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.025762	Structured	0.250630	Uncertain	0.945	0.273	0.000											-6.072	Likely Benign	0.136	Likely Benign	Likely Benign	1.45	Ambiguous	0.2	0.50	Ambiguous	0.98	Ambiguous	1.13	Destabilizing	0.461	Likely Benign	-1.00	Neutral	0.792	Possibly Damaging	0.332	Benign	-1.36	Pathogenic	0.02	Affected			0.0999	0.2291		4	3	-0.3	-14.03
c.1536A>C	E512D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E512D is not reported in ClinVar or gnomAD. Across a broad panel of in silico predictors, the majority indicate a benign effect: REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score. Only the ESM1b model assigns a pathogenic label, while Rosetta and Foldetta provide uncertain results. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) resolves to benign, and Foldetta remains inconclusive. Consequently, the variant is most likely benign, and this assessment does not contradict any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.092881	Structured	0.247079	Uncertain	0.923	0.273	0.000											-8.354	Likely Pathogenic	0.198	Likely Benign	Likely Benign	0.12	Likely Benign	0.3	1.05	Ambiguous	0.59	Ambiguous	0.00	Likely Benign	0.259	Likely Benign	-2.10	Neutral	0.016	Benign	0.012	Benign	3.34	Benign	0.23	Tolerated			0.2055	0.3089		3	2	0.0	-14.03
c.1536A>T	E512D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense change E512D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Across the broad panel of in‑silico predictors, the majority (REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) all classify the variant as benign, whereas only ESM1b predicts it as pathogenic. The high‑accuracy tools give a consistent benign signal: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also favors benign. Foldetta, which integrates FoldX‑MD and Rosetta outputs, is inconclusive. Overall, the evidence strongly supports a benign effect; this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.092881	Structured	0.247079	Uncertain	0.923	0.273	0.000											-8.354	Likely Pathogenic	0.198	Likely Benign	Likely Benign	0.12	Likely Benign	0.3	1.05	Ambiguous	0.59	Ambiguous	0.00	Likely Benign	0.259	Likely Benign	-2.10	Neutral	0.016	Benign	0.012	Benign	3.34	Benign	0.23	Tolerated			0.2055	0.3089		3	2	0.0	-14.03
c.1540A>G	I514V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I514V is catalogued in gnomAD (variant ID 6‑33438783‑A‑G) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, Rosetta, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic outcome are limited to polyPhen‑2 HumDiv and HumVar. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized reports benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields benign, while Foldetta’s stability analysis is inconclusive. Overall, the majority of evidence indicates that I514V is most likely benign, and this conclusion does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.049374	Structured	0.221408	Uncertain	0.948	0.266	0.000								6-33438783-A-G	7	4.34e-6	-5.187	Likely Benign	0.245	Likely Benign	Likely Benign	1.39	Ambiguous	0.0	0.44	Likely Benign	0.92	Ambiguous	0.89	Ambiguous	0.173	Likely Benign	-0.79	Neutral	0.914	Possibly Damaging	0.960	Probably Damaging	3.15	Benign	0.13	Tolerated	3.37	35	0.0939	0.2130		3	4	-0.3	-14.03
c.1547C>G	A516G 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant A516G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions are limited to SIFT, whereas the remaining seven tools (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default) all predict pathogenicity. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is inconclusive, SGM‑Consensus (derived from the unanimous pathogenic vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates pathogenicity, and Foldetta (combining FoldX‑MD and Rosetta outputs) is also inconclusive. No stability‑change predictions are definitive. Overall, the majority of evidence points to a pathogenic impact for A516G. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.067594	Structured	0.167423	Uncertain	0.938	0.284	0.000											-10.673	Likely Pathogenic	0.864	Likely Pathogenic	Ambiguous	0.86	Ambiguous	0.2	1.12	Ambiguous	0.99	Ambiguous	0.88	Ambiguous	0.557	Likely Pathogenic	-3.52	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	-1.31	Pathogenic	0.10	Tolerated			0.2379	0.4370		1	0	-2.2	-14.03
c.1549C>G	L517V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L517V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree that the change is deleterious: pathogenic predictions come from SGM‑Consensus, REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM, while benign predictions are made by SIFT and AlphaMissense‑Optimized; the remaining tools (Rosetta, Foldetta, AlphaMissense‑Default) are uncertain. High‑accuracy assessments further support a pathogenic bias: AlphaMissense‑Optimized predicts benign, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is uncertain. Overall, the preponderance of evidence points to a likely pathogenic effect of the variant, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.118441	Structured	0.147645	Uncertain	0.938	0.296	0.000											-10.691	Likely Pathogenic	0.498	Ambiguous	Likely Benign	2.04	Destabilizing	0.3	1.37	Ambiguous	1.71	Ambiguous	1.14	Destabilizing	0.577	Likely Pathogenic	-2.68	Deleterious	0.998	Probably Damaging	0.992	Probably Damaging	-1.26	Pathogenic	0.17	Tolerated			0.1405	0.2398		2	1	0.4	-14.03
c.1557A>C	E519D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E519D missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, premPS, SIFT, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments further show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. With seven benign predictions versus six pathogenic ones, the overall evidence slightly favors a benign classification. This conclusion does not contradict the ClinVar status, which contains no pathogenic assertion for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.078022	Structured	0.104514	Uncertain	0.899	0.328	0.000											-8.009	Likely Pathogenic	0.723	Likely Pathogenic	Likely Benign	0.24	Likely Benign	0.0	0.40	Likely Benign	0.32	Likely Benign	0.05	Likely Benign	0.183	Likely Benign	-2.62	Deleterious	0.989	Probably Damaging	0.979	Probably Damaging	3.31	Benign	0.07	Tolerated			0.2088	0.1824		3	2	0.0	-14.03
c.1557A>T	E519D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E519D is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, SIFT, and FATHMM, while those that predict a pathogenic outcome are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicating a likely pathogenic status, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicting a benign effect. Overall, the majority of tools, including the high‑accuracy methods, lean toward a benign interpretation. This consensus does not contradict ClinVar status, as the variant is currently unreported there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.078022	Structured	0.104514	Uncertain	0.899	0.328	0.000											-8.009	Likely Pathogenic	0.723	Likely Pathogenic	Likely Benign	0.24	Likely Benign	0.0	0.40	Likely Benign	0.32	Likely Benign	0.05	Likely Benign	0.182	Likely Benign	-2.62	Deleterious	0.989	Probably Damaging	0.979	Probably Damaging	3.31	Benign	0.07	Tolerated			0.2088	0.1824		3	2	0.0	-14.03
c.1563G>C	E521D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense change E521D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Benign). Only two tools, polyPhen‑2 HumDiv and HumVar, predict a pathogenic outcome. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized scores the variant as Benign; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields Likely Benign; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, reports a Benign effect. No prediction or stability result is missing or inconclusive. Based on the collective evidence, the variant is most likely benign, and this conclusion is consistent with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.086953	Structured	0.062387	Uncertain	0.865	0.349	0.000											-4.963	Likely Benign	0.372	Ambiguous	Likely Benign	0.13	Likely Benign	0.0	0.17	Likely Benign	0.15	Likely Benign	-0.29	Likely Benign	0.227	Likely Benign	1.07	Neutral	0.986	Probably Damaging	0.989	Probably Damaging	3.40	Benign	0.92	Tolerated			0.2026	0.3721		3	2	0.0	-14.03
c.1563G>T	E521D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E521D missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) all indicate benign or likely benign. Only two tools—polyPhen‑2 HumDiv and HumVar—predict a pathogenic outcome. The high‑accuracy methods give a consistent benign signal: AlphaMissense‑Optimized is benign, the SGM‑Consensus is likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) is benign. No prediction or folding stability result is missing or inconclusive. Based on the preponderance of evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.086953	Structured	0.062387	Uncertain	0.865	0.349	0.000											-4.963	Likely Benign	0.372	Ambiguous	Likely Benign	0.13	Likely Benign	0.0	0.17	Likely Benign	0.15	Likely Benign	-0.29	Likely Benign	0.227	Likely Benign	1.07	Neutral	0.986	Probably Damaging	0.989	Probably Damaging	3.40	Benign	0.92	Tolerated			0.2026	0.3721		3	2	0.0	-14.03
c.1566A>C	E522D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E522D missense variant is not reported in ClinVar and has no gnomAD entry. Prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, Rosetta, premPS, SIFT, and ESM1b, while pathogenic predictions arise from SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support a pathogenic bias: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, whereas Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, indicates a benign effect. Overall, the balance of evidence points to a likely pathogenic impact for E522D, and this assessment does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.092881	Structured	0.046216	Uncertain	0.823	0.376	0.000											-5.385	Likely Benign	0.984	Likely Pathogenic	Likely Pathogenic	0.04	Likely Benign	0.1	-0.02	Likely Benign	0.01	Likely Benign	0.32	Likely Benign	0.494	Likely Benign	-2.65	Deleterious	0.986	Probably Damaging	0.989	Probably Damaging	-1.33	Pathogenic	0.10	Tolerated			0.1499	0.2765		3	2	0.0	-14.03
c.1566A>T	E522D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E522D missense variant is not reported in ClinVar and has no gnomAD entry. Prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, Rosetta, premPS, SIFT, and ESM1b, while pathogenic predictions arise from SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support a pathogenic bias: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, whereas Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, indicates a benign effect. Overall, the balance of evidence points to a likely pathogenic impact for E522D, and this assessment does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.092881	Structured	0.046216	Uncertain	0.823	0.376	0.000											-5.385	Likely Benign	0.984	Likely Pathogenic	Likely Pathogenic	0.04	Likely Benign	0.1	-0.02	Likely Benign	0.01	Likely Benign	0.32	Likely Benign	0.494	Likely Benign	-2.65	Deleterious	0.986	Probably Damaging	0.989	Probably Damaging	-1.33	Pathogenic	0.10	Tolerated			0.1499	0.2765		3	2	0.0	-14.03
c.1575G>C	E525D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E525D missense variant is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FATHMM, and Foldetta, whereas the majority of tools predict a pathogenic impact: SGM‑Consensus (Likely Pathogenic), premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX and Rosetta provide uncertain results and are therefore not used to weigh the overall assessment. High‑accuracy methods give a mixed picture: AlphaMissense‑Optimized reports pathogenic, the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Pathogenic, while Foldetta predicts benign. Overall, the preponderance of evidence from both general and high‑accuracy predictors points to a pathogenic effect for E525D. This conclusion does not contradict ClinVar status, as the variant is not yet classified in that database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.206376	Structured	0.023618	Uncertain	0.937	0.382	0.125											-11.207	Likely Pathogenic	0.984	Likely Pathogenic	Likely Pathogenic	0.78	Ambiguous	0.6	-0.55	Ambiguous	0.12	Likely Benign	1.00	Destabilizing	0.362	Likely Benign	-2.98	Deleterious	0.989	Probably Damaging	0.979	Probably Damaging	2.90	Benign	0.00	Affected			0.1876	0.2197		3	2	0.0	-14.03
c.1575G>T	E525D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E525D missense variant is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FATHMM, and Foldetta, whereas a majority of tools predict a pathogenic impact: SGM‑Consensus (Likely Pathogenic), premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX and Rosetta provide uncertain results and are not counted as evidence. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta as benign. Overall, the balance of evidence (nine pathogenic versus three benign predictions) indicates that the variant is most likely pathogenic, and this conclusion does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.206376	Structured	0.023618	Uncertain	0.937	0.382	0.125											-11.207	Likely Pathogenic	0.984	Likely Pathogenic	Likely Pathogenic	0.78	Ambiguous	0.6	-0.55	Ambiguous	0.12	Likely Benign	1.00	Destabilizing	0.362	Likely Benign	-2.98	Deleterious	0.989	Probably Damaging	0.979	Probably Damaging	2.90	Benign	0.00	Affected			0.1876	0.2197		3	2	0.0	-14.03
c.1585A>G	I529V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I529V is not reported in ClinVar (ClinVar status: not listed) but is present in gnomAD (gnomAD ID 6‑33438828‑A‑G). Prediction tools that uniformly indicate a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only FATHMM predicts a pathogenic outcome. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, the SGM Consensus is Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts Benign. Based on the collective predictions, the variant is most likely benign, and this conclusion is consistent with the absence of a ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.318242	Structured	0.019545	Uncertain	0.901	0.403	0.000								6-33438828-A-G	1	6.20e-7	-2.342	Likely Benign	0.068	Likely Benign	Likely Benign	0.18	Likely Benign	0.0	0.03	Likely Benign	0.11	Likely Benign	0.36	Likely Benign	0.230	Likely Benign	-0.21	Neutral	0.019	Benign	0.014	Benign	-1.24	Pathogenic	1.00	Tolerated	3.37	35	0.1043	0.3526		3	4	-0.3	-14.03
c.1594A>T	T532S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T532S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. Only FATHMM predicts a pathogenic outcome. When high‑accuracy methods are considered separately, AlphaMissense‑Optimized remains benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Benign,” and Foldetta (combining FoldX‑MD and Rosetta outputs) also reports a benign effect. No prediction or stability result is missing or inconclusive. Based on the preponderance of evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.275179	Structured	0.021478	Uncertain	0.889	0.385	0.000											0.616	Likely Benign	0.062	Likely Benign	Likely Benign	0.15	Likely Benign	0.1	-0.23	Likely Benign	-0.04	Likely Benign	-0.10	Likely Benign	0.160	Likely Benign	0.53	Neutral	0.005	Benign	0.013	Benign	-1.22	Pathogenic	1.00	Tolerated			0.2988	0.2866		1	1	-0.1	-14.03
c.1598C>G	A533G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A533G resides in the GAP domain. ClinVar has no entry for this variant, and it is not reported in gnomAD. Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, FoldX, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only FATHMM predicts a pathogenic outcome; Rosetta is uncertain and therefore not counted as evidence. High‑accuracy assessments—all of which are available—show AlphaMissense‑Optimized as Benign, SGM‑Consensus as Likely Benign, and Foldetta as Benign, reinforcing the benign consensus. Based on the collective predictions, the variant is most likely benign, and this conclusion does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.179055	Structured	0.026324	Uncertain	0.843	0.393	0.000											-3.412	Likely Benign	0.122	Likely Benign	Likely Benign	0.32	Likely Benign	0.1	0.64	Ambiguous	0.48	Likely Benign	0.33	Likely Benign	0.185	Likely Benign	-1.94	Neutral	0.258	Benign	0.099	Benign	-1.23	Pathogenic	0.23	Tolerated			0.2348	0.4737		1	0	-2.2	-14.03
c.1606T>G	L536V 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L536V is listed in ClinVar (ID 1690714.0) with an uncertain significance designation and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized; pathogenic predictions arise from REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely pathogenic verdict. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) remains uncertain. No evidence from FoldX or Rosetta alone is available. Overall, the majority of evidence points toward a pathogenic effect, which does not contradict the ClinVar uncertain status but suggests a higher likelihood of pathogenicity. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.137348	Structured	0.042188	Uncertain	0.931	0.341	0.000					Uncertain		1				-9.014	Likely Pathogenic	0.269	Likely Benign	Likely Benign	1.25	Ambiguous	0.3	1.22	Ambiguous	1.24	Ambiguous	1.20	Destabilizing	0.586	Likely Pathogenic	-2.81	Deleterious	0.998	Probably Damaging	0.992	Probably Damaging	-1.34	Pathogenic	0.09	Tolerated	3.37	34	0.1591	0.3565		2	1	0.4	-14.03	204.7	26.4	0.2	0.0	-0.2	0.2						X		Potentially Benign	Leu536 is located on an α-helix (res. Ala533-Val560) at the membrane interface. The iso-butyl group of Leu536 interacts with nearby hydrophobic residues in the preceding loop (e.g., Val526, Pro528, Cys531). In the variant simulations, the iso-propyl side chain of Val536 forms similar hydrophobic interactions as Leu536 in the WT, causing no negative structural effects.
c.1610C>G	A537G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A537G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, FoldX, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign, while polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM predict pathogenic. Uncertain results come from Rosetta, Foldetta, and premPS. The high‑accuracy consensus methods reinforce the benign assessment: AlphaMissense‑Optimized reports benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates Likely Benign, and Foldetta’s stability prediction is inconclusive. Overall, the majority of evidence supports a benign impact for A537G, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.116183	Structured	0.037313	Uncertain	0.928	0.362	0.000											-4.302	Likely Benign	0.126	Likely Benign	Likely Benign	0.40	Likely Benign	0.0	0.88	Ambiguous	0.64	Ambiguous	0.68	Ambiguous	0.290	Likely Benign	-1.85	Neutral	0.977	Probably Damaging	0.672	Possibly Damaging	-1.30	Pathogenic	0.36	Tolerated			0.2289	0.3387		1	0	-2.2	-14.03
c.1614G>C	E538D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E538D is not reported in ClinVar and is absent from gnomAD. All available in‑silico predictors classify it as benign: SIFT, PolyPhen‑2 (HumDiv and HumVar), REVEL, PROVEAN, premPS, FoldX, Rosetta, AlphaMissense‑Default, AlphaMissense‑Optimized, ESM1b, and FATHMM. No tool predicts pathogenicity. High‑accuracy assessments concur: AlphaMissense‑Optimized predicts benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates “Likely Benign”; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also reports benign. Consequently, the variant is most likely benign, and this prediction does not contradict the ClinVar status (no ClinVar entry). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.122885	Structured	0.033501	Uncertain	0.938	0.359	0.000											-2.355	Likely Benign	0.112	Likely Benign	Likely Benign	0.32	Likely Benign	0.0	0.09	Likely Benign	0.21	Likely Benign	0.16	Likely Benign	0.122	Likely Benign	-0.88	Neutral	0.002	Benign	0.005	Benign	3.35	Benign	0.30	Tolerated			0.1801	0.2352		3	2	0.0	-14.03
c.1614G>T	E538D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E538D is not reported in ClinVar and is absent from gnomAD. All available in‑silico predictors classify it as benign: SIFT, PolyPhen‑2 (HumDiv and HumVar), REVEL, PROVEAN, premPS, FoldX, Rosetta, AlphaMissense‑Default, AlphaMissense‑Optimized, ESM1b, and FATHMM. No tool predicts pathogenicity. High‑accuracy assessments concur: AlphaMissense‑Optimized predicts benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates “Likely Benign”; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also reports benign. Consequently, the variant is most likely benign, and this prediction does not contradict the ClinVar status (no ClinVar entry). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.122885	Structured	0.033501	Uncertain	0.938	0.359	0.000											-2.355	Likely Benign	0.112	Likely Benign	Likely Benign	0.32	Likely Benign	0.0	0.09	Likely Benign	0.21	Likely Benign	0.16	Likely Benign	0.122	Likely Benign	-0.88	Neutral	0.002	Benign	0.005	Benign	3.35	Benign	0.30	Tolerated			0.1801	0.2352		3	2	0.0	-14.03
c.1622C>G	A541G 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant A541G is listed in ClinVar with an uncertain significance and is present in gnomAD (ID 6‑33438865‑C‑G). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. The remaining tools (FoldX, Rosetta, Foldetta, premPS, AlphaMissense‑Default, and ESM1b) return uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta is also inconclusive. Overall, the balance of evidence leans toward a benign impact, which does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.050641	Structured	0.029947	Uncertain	0.955	0.365	0.000					Uncertain		1	6-33438865-C-G	2	1.24e-6	-7.233	In-Between	0.341	Ambiguous	Likely Benign	0.67	Ambiguous	0.0	0.94	Ambiguous	0.81	Ambiguous	0.76	Ambiguous	0.421	Likely Benign	-1.48	Neutral	0.999	Probably Damaging	0.995	Probably Damaging	-1.31	Pathogenic	0.57	Tolerated	3.37	35	0.1787	0.2428		1	0	-2.2	-14.03	170.1	23.6	0.0	0.0	0.0	0.0	X							Potentially Pathogenic	Ala541 is located on the outer surface of an α-helix (res. Ala533-Val560). The methyl group of Ala541 is on the surface and does not form any interactions. Glycine, known as an “α-helix breaker,” weakens the integrity of the helix. Indeed, in the variant simulations, the hydrogen bond formation between Gly541 and the backbone carbonyl of Ala537 is disrupted.
c.1627C>G	L543V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L543V is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated algorithms—FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—classify the variant as pathogenic. AlphaMissense‑Optimized is inconclusive (uncertain). High‑accuracy assessments further support pathogenicity: the SGM‑Consensus predicts “Likely Pathogenic,” and Foldetta, which integrates FoldX‑MD and Rosetta outputs, predicts a destabilizing, pathogenic effect. AlphaMissense‑Optimized remains uncertain. Based on the overwhelming majority of predictions, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.048328	Structured	0.020918	Uncertain	0.963	0.314	0.000											-11.561	Likely Pathogenic	0.908	Likely Pathogenic	Ambiguous	3.09	Destabilizing	0.3	2.03	Destabilizing	2.56	Destabilizing	1.28	Destabilizing	0.398	Likely Benign	-2.99	Deleterious	0.998	Probably Damaging	0.992	Probably Damaging	1.99	Pathogenic	0.01	Affected			0.1334	0.2028		2	1	0.4	-14.03
c.1644G>C	E548D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E548D variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Functional prediction tools that agree on a benign effect include REVEL, premPS, SIFT, and FATHMM, whereas a separate group predicts pathogenicity: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. Predictions that are uncertain or unavailable are FoldX, Rosetta, Foldetta, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also yields a pathogenic verdict (2 pathogenic, 1 benign, 1 uncertain). Foldetta’s stability prediction is unavailable. Overall, the majority of evidence points to a pathogenic effect, and this conclusion does not contradict the ClinVar status, which simply lacks an entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.054297	Structured	0.008632	Uncertain	0.965	0.288	0.000											-7.359	In-Between	0.992	Likely Pathogenic	Likely Pathogenic	0.74	Ambiguous	0.1	1.29	Ambiguous	1.02	Ambiguous	0.32	Likely Benign	0.254	Likely Benign	-2.85	Deleterious	0.998	Probably Damaging	0.989	Probably Damaging	3.51	Benign	0.09	Tolerated			0.1374	0.2524		3	2	0.0	-14.03
c.1644G>T	E548D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E548D variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Functional prediction tools that agree on a benign effect include REVEL, premPS, SIFT, and FATHMM, whereas a separate group predicts a pathogenic effect: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. Predictions that are uncertain or unavailable are FoldX, Rosetta, Foldetta, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also yields a pathogenic verdict (2 pathogenic, 1 benign, 1 uncertain). Foldetta’s stability prediction is unavailable. Overall, the majority of evidence points to a pathogenic impact for E548D, and this conclusion does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.054297	Structured	0.008632	Uncertain	0.965	0.288	0.000											-7.359	In-Between	0.992	Likely Pathogenic	Likely Pathogenic	0.74	Ambiguous	0.1	1.29	Ambiguous	1.02	Ambiguous	0.32	Likely Benign	0.254	Likely Benign	-2.85	Deleterious	0.998	Probably Damaging	0.989	Probably Damaging	3.51	Benign	0.09	Tolerated			0.1374	0.2524		3	2	0.0	-14.03
c.1645T>G	L549V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L549V is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include Rosetta, PROVEAN, and SIFT, whereas a majority of tools (REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default) predict a pathogenic impact. Four tools (FoldX, Foldetta, premPS, and AlphaMissense‑Optimized) give uncertain or inconclusive results. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM Consensus as Likely Pathogenic, and Foldetta as uncertain. Overall, the balance of evidence favors a pathogenic interpretation. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.025762	Structured	0.007921	Uncertain	0.955	0.281	0.000											-9.379	Likely Pathogenic	0.847	Likely Pathogenic	Ambiguous	1.22	Ambiguous	0.3	0.27	Likely Benign	0.75	Ambiguous	0.88	Ambiguous	0.544	Likely Pathogenic	-2.32	Neutral	0.998	Probably Damaging	0.992	Probably Damaging	-1.23	Pathogenic	0.21	Tolerated			0.1400	0.1860		2	1	0.4	-14.03
c.1649C>G	A550G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 A550G missense variant is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. FoldX, Rosetta, Foldetta, and premPS are inconclusive and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized predicting benign, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta outputs, is uncertain. Overall, the majority of reliable predictors indicate a pathogenic effect. This conclusion does not contradict ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.018106	Structured	0.007241	Uncertain	0.954	0.265	0.000											-15.086	Likely Pathogenic	0.776	Likely Pathogenic	Likely Benign	1.73	Ambiguous	0.0	1.82	Ambiguous	1.78	Ambiguous	0.85	Ambiguous	0.769	Likely Pathogenic	-3.79	Deleterious	0.999	Probably Damaging	0.932	Probably Damaging	-1.31	Pathogenic	0.01	Affected			0.1595	0.2758		1	0	-2.2	-14.03
c.1651C>G	L551V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L551V is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include PROVEAN, SIFT, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are REVEL, FoldX, premPS, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. Two tools give uncertain results: AlphaMissense‑Default and Foldetta. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic. Foldetta’s stability prediction is uncertain. Overall, the majority of evidence points to a pathogenic impact for L551V. This conclusion does not contradict ClinVar status, as the variant is currently unreported in that database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.009977	Structured	0.006653	Uncertain	0.960	0.254	0.000											-10.154	Likely Pathogenic	0.556	Ambiguous	Likely Benign	2.04	Destabilizing	0.0	1.41	Ambiguous	1.73	Ambiguous	1.03	Destabilizing	0.575	Likely Pathogenic	-1.39	Neutral	0.998	Probably Damaging	0.992	Probably Damaging	-1.48	Pathogenic	0.22	Tolerated			0.1376	0.2778		2	1	0.4	-14.03
c.166C>G	L56V 2D AIThe SynGAP1 missense variant L56V is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b; AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also leans benign (2 benign vs 1 pathogenic, 1 uncertain). Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for the L56V variant, and this conclusion does not contradict any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.342579	Structured	0.476218	Uncertain	0.495	0.657	0.000											-8.104	Likely Pathogenic	0.471	Ambiguous	Likely Benign										0.123	Likely Benign	-0.99	Neutral	0.458	Possibly Damaging	0.745	Possibly Damaging	3.90	Benign	0.00	Affected			0.1635	0.3655		2	1	0.4	-14.03
c.1692G>C	E564D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E564D is not reported in ClinVar and has no entries in gnomAD. Prediction tools that indicate a benign effect include FoldX, premPS, and SIFT, whereas a majority of other in silico predictors (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default) classify the change as pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. With the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic; this assessment does not contradict the ClinVar status, which currently has no classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.023534	Structured	0.038418	Uncertain	0.891	0.208	0.000											-10.184	Likely Pathogenic	0.915	Likely Pathogenic	Ambiguous	0.47	Likely Benign	0.1	1.13	Ambiguous	0.80	Ambiguous	0.26	Likely Benign	0.637	Likely Pathogenic	-2.75	Deleterious	0.994	Probably Damaging	0.979	Probably Damaging	-1.37	Pathogenic	0.07	Tolerated			0.1431	0.3354		3	2	0.0	-14.03
c.1692G>T	E564D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E564D is not reported in ClinVar and has no entries in gnomAD. Prediction tools that indicate a benign effect include FoldX, premPS, and SIFT, whereas a majority of other in silico predictors (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default) classify the change as pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. With the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic; this assessment does not contradict the ClinVar status, which currently has no classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.023534	Structured	0.038418	Uncertain	0.891	0.208	0.000											-10.184	Likely Pathogenic	0.915	Likely Pathogenic	Ambiguous	0.47	Likely Benign	0.1	1.13	Ambiguous	0.80	Ambiguous	0.26	Likely Benign	0.637	Likely Pathogenic	-2.75	Deleterious	0.994	Probably Damaging	0.979	Probably Damaging	-1.37	Pathogenic	0.07	Tolerated			0.1431	0.3354		3	2	0.0	-14.03
c.1693C>G	L565V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L565V has no ClinVar entry and is not reported in gnomAD. Prediction tools cluster into two consensus groups: benign predictions come from REVEL and FATHMM, while pathogenic predictions are made by SGM‑Consensus, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and Foldetta. Two tools (AlphaMissense‑Optimized and Rosetta) give uncertain results. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is inconclusive, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Pathogenic,” and Foldetta, which integrates FoldX‑MD and Rosetta outputs, predicts a pathogenic impact on protein stability. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.034884	Structured	0.045819	Uncertain	0.922	0.205	0.000											-11.118	Likely Pathogenic	0.833	Likely Pathogenic	Ambiguous	2.69	Destabilizing	0.0	1.37	Ambiguous	2.03	Destabilizing	1.40	Destabilizing	0.303	Likely Benign	-2.99	Deleterious	0.996	Probably Damaging	0.992	Probably Damaging	2.87	Benign	0.03	Affected			0.1558	0.2488		2	1	0.4	-14.03
c.169C>G	L57V 2D AIThe SynGAP1 missense variant L57V is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized returns Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability prediction is available. Overall, the majority of evidence points to a benign effect for the variant, and this conclusion is not contradicted by any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.254060	Structured	0.481044	Uncertain	0.554	0.642	0.000											-3.598	Likely Benign	0.256	Likely Benign	Likely Benign										0.051	Likely Benign	-0.14	Neutral	0.458	Possibly Damaging	0.745	Possibly Damaging	4.17	Benign	0.00	Affected			0.1533	0.4006		2	1	0.4	-14.03
c.1701G>C	E567D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E567D missense variant is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, SIFT, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Uncertain or unavailable results come from FoldX, Rosetta, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, while the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic outcome; Foldetta’s stability prediction is uncertain. Overall, the majority of evidence points toward a pathogenic impact, and this conclusion does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.021816	Structured	0.051008	Uncertain	0.916	0.234	0.000											-8.276	Likely Pathogenic	0.575	Likely Pathogenic	Likely Benign	0.87	Ambiguous	0.1	1.94	Ambiguous	1.41	Ambiguous	0.70	Ambiguous	0.184	Likely Benign	-2.72	Deleterious	0.996	Probably Damaging	0.989	Probably Damaging	3.41	Benign	0.21	Tolerated			0.1602	0.3426		3	2	0.0	-14.03
c.1701G>T	E567D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E567D missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic impact are SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and AlphaMissense‑Default. Uncertain or unavailable results come from FoldX, Rosetta, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, while the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic outcome; Foldetta’s stability prediction is inconclusive. Overall, the majority of pathogenic predictions outweigh the benign ones, suggesting the variant is most likely pathogenic. This conclusion is not contradicted by ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.021816	Structured	0.051008	Uncertain	0.916	0.234	0.000											-8.276	Likely Pathogenic	0.575	Likely Pathogenic	Likely Benign	0.87	Ambiguous	0.1	1.94	Ambiguous	1.41	Ambiguous	0.70	Ambiguous	0.184	Likely Benign	-2.72	Deleterious	0.996	Probably Damaging	0.989	Probably Damaging	3.41	Benign	0.21	Tolerated			0.1602	0.3426		3	2	0.0	-14.03
c.1709C>G	A570G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 A570G missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include SIFT and AlphaMissense‑Optimized. Those that predict a pathogenic effect are REVEL, Rosetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), and FATHMM. The remaining tools (FoldX, premPS, ESM1b, AlphaMissense‑Default) give uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) and Foldetta are unavailable due to mixed or uncertain outputs. Overall, the majority of evaluated tools (seven pathogenic vs. two benign) indicate that the variant is most likely pathogenic, and this assessment does not contradict ClinVar status because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.046336	Structured	0.054494	Uncertain	0.932	0.263	0.000											-7.509	In-Between	0.562	Ambiguous	Likely Benign	1.34	Ambiguous	0.1	2.12	Destabilizing	1.73	Ambiguous	0.99	Ambiguous	0.607	Likely Pathogenic	-3.62	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	-1.30	Pathogenic	0.09	Tolerated			0.1700	0.2499		1	0	-2.2	-14.03
c.1720C>G	L574V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L574V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only FATHMM predicts a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely benign, while Foldetta (combining FoldX‑MD and Rosetta outputs) yields an uncertain result. No other high‑confidence pathogenic predictions are present. Based on the preponderance of benign predictions and the lack of any ClinVar pathogenic annotation, the variant is most likely benign. This conclusion does not contradict any existing ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.083462	Structured	0.026427	Uncertain	0.927	0.246	0.000											-5.559	Likely Benign	0.105	Likely Benign	Likely Benign	0.78	Ambiguous	0.1	0.37	Likely Benign	0.58	Ambiguous	0.25	Likely Benign	0.149	Likely Benign	-0.40	Neutral	0.004	Benign	0.003	Benign	-1.27	Pathogenic	0.29	Tolerated			0.1481	0.2978		2	1	0.4	-14.03
c.1730C>G	A577G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A577G is listed in ClinVar as Benign (ClinVar ID 1010280.0) and is present in gnomAD (ID 6‑33440782‑C‑G). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Predictions that are inconclusive (FoldX, Rosetta, Foldetta, premPS) are treated as unavailable. High‑accuracy methods give a benign verdict: AlphaMissense‑Optimized is benign, the SGM‑Consensus is Likely Benign, and Foldetta is uncertain. Overall, the majority of reliable predictions support a benign impact, which is consistent with the ClinVar status and does not contradict it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.113710	Structured	0.019074	Uncertain	0.913	0.239	0.000					Benign/Likely benign		2	6-33440782-C-G	1	6.20e-7	-5.717	Likely Benign	0.268	Likely Benign	Likely Benign	0.83	Ambiguous	0.0	1.02	Ambiguous	0.93	Ambiguous	0.86	Ambiguous	0.443	Likely Benign	-1.84	Neutral	0.997	Probably Damaging	0.990	Probably Damaging	-1.31	Pathogenic	0.31	Tolerated	3.37	34	0.2120	0.3780		1	0	-2.2	-14.03	158.7	23.6	0.0	0.0	0.0	0.0						X		Potentially Benign	Ala577 is located near the end and outer surface of an α-helix (res. Arg563-Glu578), where its methyl group does not form any particular interactions in the WT simulations. The introduced residue, glycine, is known as an “α-helix breaker.” However, the residue swap caused only minor helix shortening in one of the replica simulations for the variant system. Regardless, the residue swap seems to be well tolerated based on the variant simulations.
c.1734G>C	E578D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E578D is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM; AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) leans toward benign (2 benign vs 1 pathogenic votes), and Foldetta also predicts benign stability. No prediction or folding result is missing or inconclusive. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.059222	Structured	0.020971	Uncertain	0.902	0.240	0.000											-4.366	Likely Benign	0.447	Ambiguous	Likely Benign	0.46	Likely Benign	0.1	0.15	Likely Benign	0.31	Likely Benign	-0.05	Likely Benign	0.318	Likely Benign	-0.53	Neutral	0.989	Probably Damaging	0.979	Probably Damaging	-1.43	Pathogenic	0.33	Tolerated			0.1561	0.3554		3	2	0.0	-14.03
c.1734G>T	E578D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E578D missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM; AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) resolves to benign (2 benign vs 1 pathogenic votes), and Foldetta predicts a benign stability change. No prediction or stability result is missing or inconclusive. Overall, the majority of evidence indicates that the variant is most likely benign, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.059222	Structured	0.020971	Uncertain	0.902	0.240	0.000											-4.366	Likely Benign	0.447	Ambiguous	Likely Benign	0.46	Likely Benign	0.1	0.15	Likely Benign	0.31	Likely Benign	-0.05	Likely Benign	0.318	Likely Benign	-0.53	Neutral	0.989	Probably Damaging	0.979	Probably Damaging	-1.43	Pathogenic	0.33	Tolerated			0.1561	0.3554		3	2	0.0	-14.03
c.1746G>C	E582D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E582D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two consensus groups: a benign group comprising REVEL, premPS, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized, and a pathogenic group containing polyPhen‑2 HumDiv and polyPhen‑2 HumVar. Remaining tools (FoldX, Rosetta, ESM1b, AlphaMissense‑Default) yield uncertain results and are treated as unavailable. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) leans toward benign, and Foldetta indicates no significant destabilization. Consequently, the variant is most likely benign, and this assessment does not contradict the ClinVar status, which currently has no entry for this change. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.102787	Structured	0.033838	Uncertain	0.845	0.235	0.000											-7.974	In-Between	0.520	Ambiguous	Likely Benign	0.57	Ambiguous	0.2	0.95	Ambiguous	0.76	Ambiguous	0.40	Likely Benign	0.093	Likely Benign	-1.63	Neutral	0.986	Probably Damaging	0.989	Probably Damaging	3.22	Benign	0.27	Tolerated			0.1481	0.2236		3	2	0.0	-14.03
c.1746G>T	E582D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E582D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two consensus groups: a benign group comprising REVEL, premPS, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized, and a pathogenic group consisting of polyPhen‑2 HumDiv and polyPhen‑2 HumVar. Remaining tools (FoldX, Rosetta, ESM1b, AlphaMissense‑Default) yield uncertain results. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized predicts benign; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive because two of the four inputs are uncertain; Foldetta, which integrates FoldX‑MD and Rosetta outputs, also reports an uncertain stability change. Consequently, the preponderance of evidence points to a benign effect. This conclusion aligns with the absence of a ClinVar assertion, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.102787	Structured	0.033838	Uncertain	0.845	0.235	0.000											-7.974	In-Between	0.520	Ambiguous	Likely Benign	0.57	Ambiguous	0.2	0.95	Ambiguous	0.76	Ambiguous	0.40	Likely Benign	0.093	Likely Benign	-1.63	Neutral	0.986	Probably Damaging	0.989	Probably Damaging	3.22	Benign	0.27	Tolerated			0.1481	0.2236		3	2	0.0	-14.03
c.1750A>G	I584V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I584V is catalogued in gnomAD (ID 6‑33440802‑A‑G) but has no ClinVar entry. Prediction tools that agree on a benign effect include REVEL, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are premPS, polyPhen‑2 HumDiv, and FATHMM. Two tools (FoldX and ESM1b) returned uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also favors benign (2 benign vs. 1 pathogenic vote), and Foldetta predicts benign stability. Overall, the majority of evidence points to a benign impact. This conclusion does not contradict ClinVar status, as no ClinVar classification is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.059222	Structured	0.046673	Uncertain	0.846	0.244	0.000								6-33440802-A-G	1	6.20e-7	-7.562	In-Between	0.234	Likely Benign	Likely Benign	0.67	Ambiguous	0.1	0.29	Likely Benign	0.48	Likely Benign	1.16	Destabilizing	0.405	Likely Benign	-0.95	Neutral	0.642	Possibly Damaging	0.349	Benign	-1.18	Pathogenic	0.18	Tolerated	3.37	34	0.1007	0.2659		3	4	-0.3	-14.03
c.1754C>G	A585G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A585G is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, SIFT, ESM1b, and AlphaMissense‑Optimized, while pathogenic predictions arise from polyPhen‑2 (HumDiv and HumVar), FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, whereas the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive due to a 2‑to‑2 split, and Foldetta reports an uncertain stability change. No evidence from these high‑confidence tools supports pathogenicity. Overall, the balance of evidence favors a benign effect for A585G, and this conclusion is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.060549	Structured	0.055884	Uncertain	0.880	0.244	0.000											-3.879	Likely Benign	0.629	Likely Pathogenic	Likely Benign	1.62	Ambiguous	0.0	1.94	Ambiguous	1.78	Ambiguous	0.59	Ambiguous	0.384	Likely Benign	-1.16	Neutral	0.999	Probably Damaging	0.995	Probably Damaging	-1.33	Pathogenic	0.24	Tolerated			0.1724	0.2299		1	0	-2.2	-14.03
c.175C>G	L59V 2D AIThe SynGAP1 missense variant L59V is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for this variant. This conclusion is consistent with the absence of a ClinVar classification, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.212910	Structured	0.484882	Uncertain	0.510	0.668	0.000											-4.465	Likely Benign	0.588	Likely Pathogenic	Likely Benign										0.049	Likely Benign	-1.15	Neutral	0.458	Possibly Damaging	0.745	Possibly Damaging	3.36	Benign	0.00	Affected			0.1508	0.3217		2	1	0.4	-14.03
c.1762C>G	L588V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L588V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: SIFT classifies it as benign, whereas the remaining 13 tools (REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus) predict pathogenicity. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. Taken together, the overwhelming majority of evidence points to a pathogenic effect for L588V. This conclusion is consistent with the absence of a ClinVar entry, so there is no contradiction with existing clinical annotations. Thus, the variant is most likely pathogenic, with no contradiction to ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.038042	Structured	0.082229	Uncertain	0.887	0.214	0.000											-10.374	Likely Pathogenic	0.897	Likely Pathogenic	Ambiguous	3.61	Destabilizing	0.4	2.81	Destabilizing	3.21	Destabilizing	1.24	Destabilizing	0.533	Likely Pathogenic	-2.99	Deleterious	0.998	Probably Damaging	0.992	Probably Damaging	-1.28	Pathogenic	0.08	Tolerated			0.1422	0.2228		2	1	0.4	-14.03
c.1765A>G	I589V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 I589V missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include PROVEAN, SIFT, ESM1b, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are REVEL, polyPhen‑2 (HumDiv and HumVar), and FATHMM. The remaining tools—FoldX, Rosetta, Foldetta, premPS, and AlphaMissense‑Default—return uncertain or inconclusive results. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is benign; and Foldetta is uncertain. Taken together, the majority of evidence, including the high‑accuracy predictions, points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation and does not contradict any existing clinical database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.018415	Structured	0.084536	Uncertain	0.927	0.214	0.000											-6.966	Likely Benign	0.464	Ambiguous	Likely Benign	0.98	Ambiguous	0.0	0.78	Ambiguous	0.88	Ambiguous	0.96	Ambiguous	0.535	Likely Pathogenic	-1.00	Neutral	0.969	Probably Damaging	0.960	Probably Damaging	-1.50	Pathogenic	0.31	Tolerated			0.1356	0.3568		4	3	-0.3	-14.03
c.1772C>G	A591G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A591G is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote). Only PROVEAN predicts a pathogenic outcome. Predictions that are inconclusive or unavailable are FoldX, Rosetta, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus as Likely Benign, and Foldetta as uncertain. Overall, the majority of evidence points to a benign impact for A591G, and this conclusion does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.018787	Structured	0.093848	Uncertain	0.882	0.185	0.000											-6.596	Likely Benign	0.233	Likely Benign	Likely Benign	1.22	Ambiguous	0.2	1.74	Ambiguous	1.48	Ambiguous	0.83	Ambiguous	0.142	Likely Benign	-2.77	Deleterious	0.007	Benign	0.009	Benign	3.60	Benign	0.16	Tolerated			0.2117	0.2228		1	0	-2.2	-14.03
c.1777C>G	L593V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 L593V missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic impact are FoldX, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. Uncertain or inconclusive results come from Rosetta, Foldetta, and AlphaMissense‑Default. High‑accuracy assessments: AlphaMissense‑Optimized classifies the variant as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a pathogenic prediction; Foldetta, which integrates FoldX‑MD and Rosetta outputs, is uncertain. Overall, the majority of evidence (six pathogenic vs. four benign) points to a pathogenic effect. This conclusion is consistent with the lack of ClinVar annotation and gnomAD presence, so there is no contradiction with existing database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.009728	Structured	0.110534	Uncertain	0.941	0.151	0.000											-10.327	Likely Pathogenic	0.551	Ambiguous	Likely Benign	2.81	Destabilizing	0.2	1.10	Ambiguous	1.96	Ambiguous	1.39	Destabilizing	0.268	Likely Benign	-2.59	Deleterious	0.998	Probably Damaging	0.992	Probably Damaging	3.04	Benign	0.12	Tolerated			0.1599	0.3577		2	1	0.4	-14.03
c.1783C>G	L595V 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L595V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL, Rosetta, and FATHMM, while pathogenic calls are made by premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Predictions marked uncertain include FoldX, Foldetta, and AlphaMissense‑Optimized. High‑accuracy consensus methods give a clearer picture: AlphaMissense‑Optimized is inconclusive, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is also inconclusive. Overall, the majority of evidence points toward a pathogenic effect, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.015344	Structured	0.128444	Uncertain	0.920	0.150	0.000											-13.490	Likely Pathogenic	0.905	Likely Pathogenic	Ambiguous	1.29	Ambiguous	0.1	0.24	Likely Benign	0.77	Ambiguous	1.01	Destabilizing	0.398	Likely Benign	-2.99	Deleterious	0.998	Probably Damaging	0.992	Probably Damaging	2.78	Benign	0.01	Affected			0.1441	0.3406		2	1	0.4	-14.03
c.1792C>G	L598V 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L598V is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Prediction tools that classify the variant as benign include REVEL, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic predictions are made by premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely pathogenic effect. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as inconclusive. Overall, the majority of evidence points to a pathogenic impact, which contrasts with the ClinVar designation of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.007259	Structured	0.147872	Uncertain	0.953	0.154	0.000					Uncertain		1				-10.002	Likely Pathogenic	0.578	Likely Pathogenic	Likely Benign	1.89	Ambiguous	0.1	1.58	Ambiguous	1.74	Ambiguous	1.01	Destabilizing	0.221	Likely Benign	-2.92	Deleterious	0.944	Possibly Damaging	0.786	Possibly Damaging	3.21	Benign	0.02	Affected	3.37	35	0.1082	0.1795		2	1	0.4	-14.03	218.4	29.6	0.0	0.0	0.8	0.0						X		Potentially Benign	The iso-butyl side chain of Leu598, located on an α helix (res. Glu582-Met603), packs hydrophobically with other hydrophobic residues in the inter-helix space (e.g., Ile602, Phe594, Ile510).In the variant simulations, Val598, which has similar size and physicochemical properties to leucine, resides in the inter-helix hydrophobic space in a similar manner to Leu598 in the WT. This causes no negative effects on the protein structure.
c.17C>G	A6G 2D AIThe SynGAP1 missense variant A6G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.566480	Disordered	0.549054	Binding	0.377	0.920	0.875											-2.786	Likely Benign	0.097	Likely Benign	Likely Benign										0.107	Likely Benign	0.31	Neutral	0.052	Benign	0.004	Benign	4.08	Benign	0.00	Affected			0.2139	0.4369		1	0	-2.2	-14.03
c.1802C>G	A601G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 A601G missense variant is listed in gnomAD (ID 6‑33440854‑C‑G) but has no ClinVar entry. Prediction tools that agree on a benign effect are FATHMM and AlphaMissense‑Optimized; those that agree on a pathogenic effect are REVEL, FoldX, Rosetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b. The high‑accuracy consensus methods give a pathogenic verdict: the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is also pathogenic. AlphaMissense‑Default and premPS are uncertain, and no evidence is available from other folding‑stability tools. Overall, the preponderance of evidence points to a pathogenic impact for A601G, and this assessment does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.008895	Structured	0.174517	Uncertain	0.955	0.156	0.000								6-33440854-C-G	1	6.19e-7	-11.772	Likely Pathogenic	0.543	Ambiguous	Likely Benign	2.03	Destabilizing	0.0	2.31	Destabilizing	2.17	Destabilizing	0.94	Ambiguous	0.511	Likely Pathogenic	-3.98	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	2.55	Benign	0.01	Affected	3.37	35	0.2337	0.4370		0	1	-2.2	-14.03
c.1804A>G	I602V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 I602V missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the change as benign include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are premPS, polyPhen‑2 HumDiv, SIFT, and FATHMM. Uncertain or inconclusive results come from FoldX, Rosetta, and Foldetta. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also predicts benign, while Foldetta’s stability analysis remains uncertain. Overall, the majority of evidence points to a benign impact. This conclusion is not contradicted by any ClinVar annotation, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.010221	Structured	0.186541	Uncertain	0.963	0.171	0.000											-6.317	Likely Benign	0.075	Likely Benign	Likely Benign	1.24	Ambiguous	0.0	0.78	Ambiguous	1.01	Ambiguous	1.01	Destabilizing	0.309	Likely Benign	-0.84	Neutral	0.528	Possibly Damaging	0.179	Benign	-1.89	Pathogenic	0.03	Affected			0.1173	0.3326		4	3	-0.3	-14.03
c.1819C>G	L607V 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L607V is listed in ClinVar with an uncertain significance (ClinVar ID 1450275.0) and is present in gnomAD (ID 6‑33440871‑C‑G). Prediction tools that agree on a benign effect include only AlphaMissense‑Optimized. All other evaluated algorithms—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—predict a pathogenic impact. High‑accuracy assessments further support this: AlphaMissense‑Optimized reports benign, whereas the SGM‑Consensus, derived from the majority of pathogenic predictions, indicates pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta outputs, is inconclusive and therefore not considered evidence. Overall, the preponderance of computational evidence points to a pathogenic effect for L607V, a conclusion that contrasts with the current ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.048328	Structured	0.194229	Uncertain	0.869	0.250	0.000					Uncertain		2	6-33440871-C-G	2	1.24e-6	-11.190	Likely Pathogenic	0.637	Likely Pathogenic	Likely Benign	1.04	Ambiguous	0.2	1.36	Ambiguous	1.20	Ambiguous	0.90	Ambiguous	0.715	Likely Pathogenic	-2.99	Deleterious	0.985	Probably Damaging	0.992	Probably Damaging	-1.50	Pathogenic	0.01	Affected	3.37	35	0.1634	0.3577		2	1	0.4	-14.03	216.3	28.1	0.1	0.0	0.9	0.2				X				Potentially Benign	Leu607 is located in a short helical region (res. Ser606-Phe608) within an α-α loop connecting two α helices (res. Glu582-Met603 and res. Glu617-Asn635). In the WT simulations, the iso-butyl side chain of Leu607 does not interact with any other residues, but it could potentially interact directly with Ras due to its location at the GAP domain.In the variant simulations, Val607, which has similar size and physicochemical properties to leucine, does not cause any negative effects on the protein structure. However, due to its location at the GAP-Ras interface, the residue swap could affect the complex formation with the GTPase, but this cannot be investigated using solvent-only simulations.
c.1828C>G	L610V 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L610V is reported in gnomAD (ID 6‑33440880‑C‑G) but has no ClinVar entry. Functional prediction tools largely agree on a deleterious effect: pathogenic calls are made by REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM, while only AlphaMissense‑Optimized predicts a benign outcome. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Pathogenic. High‑accuracy assessments further support this view: AlphaMissense‑Optimized indicates benign, whereas the SGM Consensus remains pathogenic and Foldetta (combining FoldX‑MD and Rosetta) is inconclusive. With the overwhelming majority of tools predicting pathogenicity and no ClinVar evidence to contradict this, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.271506	Structured	0.209504	Uncertain	0.888	0.253	0.000								6-33440880-C-G	3	1.86e-6	-11.304	Likely Pathogenic	0.474	Ambiguous	Likely Benign	2.24	Destabilizing	0.3	0.76	Ambiguous	1.50	Ambiguous	1.21	Destabilizing	0.740	Likely Pathogenic	-2.86	Deleterious	0.985	Probably Damaging	0.992	Probably Damaging	-1.46	Pathogenic	0.01	Affected	3.37	35	0.1515	0.3039		1	2	0.4	-14.03
c.1839G>C	E613D 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant E613D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, Rosetta, premPS, and SIFT, while pathogenic predictions arise from SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default. Three tools—FoldX, Foldetta, and AlphaMissense‑Optimized—return uncertain or inconclusive results. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is uncertain. Overall, the majority of evidence points to a pathogenic impact for E613D. This conclusion is consistent with the lack of ClinVar annotation and does not contradict any existing database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.275179	Structured	0.193489	Uncertain	0.816	0.254	0.000											-8.795	Likely Pathogenic	0.842	Likely Pathogenic	Ambiguous	0.67	Ambiguous	0.3	0.48	Likely Benign	0.58	Ambiguous	0.13	Likely Benign	0.474	Likely Benign	-2.79	Deleterious	0.989	Probably Damaging	0.979	Probably Damaging	-1.27	Pathogenic	0.15	Tolerated			0.1998	0.4000		3	2	0.0	-14.03
c.1839G>T	E613D 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant E613D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, Rosetta, premPS, and SIFT, while pathogenic predictions arise from SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default. Three tools—FoldX, Foldetta, and AlphaMissense‑Optimized—return uncertain or inconclusive results. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is uncertain. Overall, the majority of evidence points to a pathogenic impact for E613D. This conclusion is consistent with the lack of ClinVar annotation and does not contradict any existing database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.275179	Structured	0.193489	Uncertain	0.816	0.254	0.000											-8.795	Likely Pathogenic	0.842	Likely Pathogenic	Ambiguous	0.67	Ambiguous	0.3	0.48	Likely Benign	0.58	Ambiguous	0.13	Likely Benign	0.474	Likely Benign	-2.79	Deleterious	0.989	Probably Damaging	0.979	Probably Damaging	-1.27	Pathogenic	0.15	Tolerated			0.1998	0.4000		3	2	0.0	-14.03
c.183G>C	E61D 2D AIThe SynGAP1 missense variant E61D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumVar and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. The variant’s predicted benign status does not contradict ClinVar, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.352862	Structured	0.477329	Uncertain	0.518	0.699	0.125											-4.394	Likely Benign	0.231	Likely Benign	Likely Benign										0.035	Likely Benign	-0.29	Neutral	0.267	Benign	0.585	Possibly Damaging	4.11	Benign	0.00	Affected			0.1895	0.3851		3	2	0.0	-14.03
c.183G>T	E61D 2D AIThe SynGAP1 missense variant E61D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumVar and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. The variant’s predicted benign status does not contradict ClinVar, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.352862	Structured	0.477329	Uncertain	0.518	0.699	0.125											-4.394	Likely Benign	0.231	Likely Benign	Likely Benign										0.035	Likely Benign	-0.29	Neutral	0.267	Benign	0.585	Possibly Damaging	4.11	Benign	0.00	Affected			0.1895	0.3851		3	2	0.0	-14.03
c.1851G>C	E617D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense change E617D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that classify the variant as benign include REVEL, FoldX, premPS, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized scores the variant as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a “Likely Benign” verdict; and Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, also reports a benign effect. Based on the preponderance of evidence from both general and high‑accuracy predictors, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.111485	Structured	0.155123	Uncertain	0.877	0.240	0.000											-1.349	Likely Benign	0.241	Likely Benign	Likely Benign	0.12	Likely Benign	0.1	0.80	Ambiguous	0.46	Likely Benign	0.07	Likely Benign	0.322	Likely Benign	-0.01	Neutral	0.994	Probably Damaging	0.979	Probably Damaging	-1.35	Pathogenic	0.88	Tolerated	3.37	35	0.1854	0.3386		2	3	0.0	-14.03
c.1851G>T	E617D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E617D is listed in ClinVar with an uncertain significance (ID 2584916.0) and is not reported in gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, FoldX, Foldetta, premPS, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score all indicate benign or likely benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and FATHMM predict a pathogenic impact, while Rosetta remains inconclusive. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized is benign; the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is likely benign; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts benign. Overall, the preponderance of evidence supports a benign classification, which does not contradict the current ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.111485	Structured	0.155123	Uncertain	0.877	0.240	0.000					Uncertain		1				-1.349	Likely Benign	0.241	Likely Benign	Likely Benign	0.12	Likely Benign	0.1	0.80	Ambiguous	0.46	Likely Benign	0.07	Likely Benign	0.322	Likely Benign	-0.01	Neutral	0.994	Probably Damaging	0.979	Probably Damaging	-1.35	Pathogenic	0.88	Tolerated	3.37	35	0.1854	0.3386		2	3	0.0	-14.03
c.1855A>T	T619S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T619S is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Prediction tools that agree on a benign effect include only AlphaMissense‑Optimized. All other evaluated algorithms—SGM‑Consensus (Likely Pathogenic), REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—consistently predict a pathogenic impact. High‑accuracy assessments further support this view: AlphaMissense‑Optimized reports a benign outcome, whereas the SGM Consensus, derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates pathogenicity. Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, yields an uncertain result. Overall, the majority of evidence points to a pathogenic effect for T619S, and this conclusion does not contradict the ClinVar designation of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.219301	Structured	0.119723	Uncertain	0.929	0.237	0.000					Uncertain		1				-8.608	Likely Pathogenic	0.677	Likely Pathogenic	Likely Benign	1.09	Ambiguous	0.2	1.35	Ambiguous	1.22	Ambiguous	0.85	Ambiguous	0.602	Likely Pathogenic	-3.42	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	-1.30	Pathogenic	0.05	Affected	3.37	35	0.3255	0.2860		1	1	-0.1	-14.03
c.1856C>G	T619S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 T619S missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include only AlphaMissense‑Optimized. All other evaluated predictors (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default) uniformly predict a pathogenic impact. High‑accuracy assessments further support this: AlphaMissense‑Optimized remains benign, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels the variant as Likely Pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, yields an uncertain result. No other high‑confidence stability predictions are available. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status, as none is assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.219301	Structured	0.119723	Uncertain	0.929	0.237	0.000											-8.608	Likely Pathogenic	0.677	Likely Pathogenic	Likely Benign	1.09	Ambiguous	0.2	1.35	Ambiguous	1.22	Ambiguous	0.85	Ambiguous	0.523	Likely Pathogenic	-3.42	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	-1.30	Pathogenic	0.05	Affected	3.37	35	0.3255	0.2860		1	1	-0.1	-14.03
c.1864A>T	T622S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T622S is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from SIFT and AlphaMissense‑Optimized, while pathogenic predictions arise from REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized labeling the variant as benign, whereas the SGM‑Consensus predicts it to be likely pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta outputs, yields an uncertain result. No other folding‑stability tools provide conclusive evidence. Overall, the preponderance of predictions, including the SGM‑Consensus, indicates that T622S is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.268042	Structured	0.071403	Uncertain	0.957	0.198	0.000											-9.840	Likely Pathogenic	0.669	Likely Pathogenic	Likely Benign	0.78	Ambiguous	0.1	1.36	Ambiguous	1.07	Ambiguous	0.80	Ambiguous	0.705	Likely Pathogenic	-3.52	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	-1.50	Pathogenic	0.09	Tolerated			0.2523	0.3183		1	1	-0.1	-14.03
c.1865C>G	T622S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T622S is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from SIFT and AlphaMissense‑Optimized, while pathogenic predictions arise from REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized labeling the variant as benign, whereas the SGM‑Consensus predicts it to be likely pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta outputs, yields an uncertain result. No other folding‑stability tools provide conclusive evidence. Overall, the preponderance of predictions, including the SGM‑Consensus, indicates that T622S is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.268042	Structured	0.071403	Uncertain	0.957	0.198	0.000											-9.840	Likely Pathogenic	0.669	Likely Pathogenic	Likely Benign	0.78	Ambiguous	0.1	1.36	Ambiguous	1.07	Ambiguous	0.80	Ambiguous	0.595	Likely Pathogenic	-3.52	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	-1.50	Pathogenic	0.09	Tolerated			0.2523	0.3183		1	1	-0.1	-14.03
c.1867C>G	L623V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L623V is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only REVEL, whereas the majority of tools predict a pathogenic impact: SGM‑Consensus, FoldX, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Rosetta and AlphaMissense‑Optimized give uncertain results. High‑accuracy assessments further support pathogenicity: the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic, and AlphaMissense‑Optimized remains uncertain. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.175930	Structured	0.060667	Uncertain	0.962	0.211	0.000											-12.802	Likely Pathogenic	0.896	Likely Pathogenic	Ambiguous	3.96	Destabilizing	0.3	1.84	Ambiguous	2.90	Destabilizing	1.45	Destabilizing	0.416	Likely Benign	-2.99	Deleterious	0.998	Probably Damaging	0.992	Probably Damaging	1.60	Pathogenic	0.01	Affected			0.1653	0.3588		2	1	0.4	-14.03
c.1870A>T	T624S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 T624S missense variant is not reported in ClinVar (status: None) and has no entry in gnomAD. Prediction tools that agree on a benign effect include FoldX, Foldetta, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Rosetta and premPS are uncertain and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as benign. Overall, the majority of evidence points to a pathogenic impact, and this conclusion does not contradict any ClinVar annotation (none is present). Thus, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.137348	Structured	0.052894	Uncertain	0.962	0.217	0.000											-13.314	Likely Pathogenic	0.766	Likely Pathogenic	Likely Benign	-0.10	Likely Benign	0.1	0.95	Ambiguous	0.43	Likely Benign	0.69	Ambiguous	0.761	Likely Pathogenic	-3.93	Deleterious	0.826	Possibly Damaging	0.789	Possibly Damaging	-1.43	Pathogenic	0.01	Affected			0.2326	0.2813		1	1	-0.1	-14.03
c.1871C>G	T624S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 T624S missense variant is not reported in ClinVar (status: None) and has no entry in gnomAD. Prediction tools that agree on a benign effect include FoldX, Foldetta, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Rosetta and premPS are uncertain and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as benign. Overall, the majority of evidence points to a pathogenic impact, and this conclusion does not contradict any ClinVar annotation (none is present). Thus, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.137348	Structured	0.052894	Uncertain	0.962	0.217	0.000											-13.314	Likely Pathogenic	0.766	Likely Pathogenic	Likely Benign	-0.10	Likely Benign	0.1	0.95	Ambiguous	0.43	Likely Benign	0.69	Ambiguous	0.734	Likely Pathogenic	-3.93	Deleterious	0.826	Possibly Damaging	0.789	Possibly Damaging	-1.43	Pathogenic	0.01	Affected			0.2326	0.2813		1	1	-0.1	-14.03
c.1873C>G	L625V 2D AISynGAP1 missense variant L625V is listed in ClinVar with an uncertain significance (ClinVar ID 3392716.0) and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and FATHMM, while pathogenic predictions are made by premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. Four tools (FoldX, Rosetta, Foldetta, AlphaMissense‑Optimized) give inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta as uncertain. Overall, the majority of evidence points toward a pathogenic effect, which does not contradict the ClinVar uncertain status but suggests a higher likelihood of pathogenicity. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.229226	Structured	0.045896	Uncertain	0.966	0.215	0.000					Uncertain		1				-11.319	Likely Pathogenic	0.833	Likely Pathogenic	Ambiguous	1.80	Ambiguous	0.7	1.69	Ambiguous	1.75	Ambiguous	1.42	Destabilizing	0.480	Likely Benign	-2.96	Deleterious	0.998	Probably Damaging	0.992	Probably Damaging	3.07	Benign	0.01	Affected			0.1306	0.3427		2	1	0.4	-14.03
c.1876A>G	I626V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I626V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. Predictions that are uncertain or unavailable are AlphaMissense‑Default, FoldX, Rosetta, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus also indicates a likely benign outcome, while Foldetta’s stability analysis is inconclusive. Based on the overall consensus of the available predictions, the variant is most likely benign, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.109221	Structured	0.040732	Uncertain	0.970	0.223	0.000											-6.636	Likely Benign	0.398	Ambiguous	Likely Benign	1.24	Ambiguous	0.0	1.06	Ambiguous	1.15	Ambiguous	0.80	Ambiguous	0.182	Likely Benign	-0.80	Neutral	0.969	Probably Damaging	0.960	Probably Damaging	3.33	Benign	0.13	Tolerated			0.1003	0.2891		4	3	-0.3	-14.03
c.1880C>G	A627G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A627G is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect comprise SGM‑Consensus, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. FoldX and Foldetta are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, while the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic. Foldetta remains uncertain. Overall, the majority of evidence points to a pathogenic impact, and this conclusion does not contradict the lack of ClinVar annotation. Thus, the variant is most likely pathogenic based on current predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.100716	Structured	0.037862	Uncertain	0.970	0.210	0.000											-11.716	Likely Pathogenic	0.640	Likely Pathogenic	Likely Benign	1.38	Ambiguous	0.1	2.07	Destabilizing	1.73	Ambiguous	1.25	Destabilizing	0.458	Likely Benign	-3.96	Deleterious	0.997	Probably Damaging	0.876	Possibly Damaging	2.51	Benign	0.01	Affected			0.1921	0.2990		1	0	-2.2	-14.03
c.1888A>G	I630V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I630V is listed in ClinVar as Benign and is present in gnomAD (variant ID 6‑33440940‑A‑G). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only FATHMM predicts a pathogenic outcome; all other tools (FoldX, Rosetta, Foldetta, premPS, ESM1b) return uncertain or inconclusive results. The high‑accuracy consensus (SGM Consensus) derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN yields a benign majority (2 benign vs. 1 pathogenic, 1 uncertain). AlphaMissense‑Optimized also predicts benign. Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, is uncertain. Taken together, the overwhelming majority of predictions support a benign effect, and this conclusion aligns with the ClinVar designation. Thus, the variant is most likely benign, with no contradiction to the ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.040537	Structured	0.036106	Uncertain	0.966	0.236	0.000					Benign/Likely benign		4	6-33440940-A-G	59	3.66e-5	-7.264	In-Between	0.145	Likely Benign	Likely Benign	1.33	Ambiguous	0.0	0.94	Ambiguous	1.14	Ambiguous	0.64	Ambiguous	0.143	Likely Benign	-0.38	Neutral	0.018	Benign	0.011	Benign	-1.37	Pathogenic	0.35	Tolerated	3.37	34	0.0960	0.2891		4	3	-0.3	-14.03	235.0	26.2	-0.1	0.0	-0.3	0.1						X		Potentially Benign	The sec-butyl side chain of Ile630, located in an α helix (res. Glu617-Asn635), packs with hydrophobic residues (e.g., Phe594, Leu633, Ile626, Ile602) in the hydrophobic inter-helix space between two α helices (res. Glu617-Asn635 and res. Glu582-Met603).In the variant simulations, the iso-propyl side chain of Val630, which shares a similar size and physicochemical properties with Ile630 in the WT, maintains similar interactions in the inter-helix space. Although no negative structural effects are observed during the simulations, the implications of the residue swap on the complex formation with the GTPase, due to its location, cannot be investigated using solvent-only simulations.
c.1897C>G	L633V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L633V is not reported in ClinVar and is present in the gnomAD database (ID 6‑33440949‑C‑G). Prediction tools that indicate a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect comprise FoldX, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, SGM‑Consensus, and Foldetta; the Rosetta score is uncertain and therefore not considered. High‑accuracy methods give a pathogenic consensus: AlphaMissense‑Optimized predicts benign, but the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) and Foldetta both predict pathogenic. Overall, the majority of evidence supports a pathogenic impact for L633V, and this assessment does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.045352	Structured	0.045407	Uncertain	0.952	0.252	0.000								6-33440949-C-G	1	6.20e-7	-9.992	Likely Pathogenic	0.760	Likely Pathogenic	Likely Benign	2.32	Destabilizing	0.2	1.71	Ambiguous	2.02	Destabilizing	1.32	Destabilizing	0.327	Likely Benign	-2.99	Deleterious	0.996	Probably Damaging	0.992	Probably Damaging	2.86	Benign	0.03	Affected	3.37	34	0.1517	0.2766		1	2	0.4	-14.03
c.189G>C	E63D 2D AIThe SynGAP1 missense variant E63D is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, ESM1b, and FATHMM. Those that predict a pathogenic effect are polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized scores the variant as benign, and the SGM‑Consensus also reports it as likely benign. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of computational evidence points to a benign effect, and this conclusion does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.429200	Structured	0.474807	Uncertain	0.494	0.739	0.125											-3.821	Likely Benign	0.594	Likely Pathogenic	Likely Benign										0.066	Likely Benign	-0.83	Neutral	0.267	Benign	0.585	Possibly Damaging	3.98	Benign	0.00	Affected			0.1524	0.4130		3	2	0.0	-14.03
c.189G>T	E63D 2D AIThe SynGAP1 missense variant E63D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, polyPhen‑2 HumDiv, ESM1b, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions come from polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority of the high‑accuracy tools) also indicates benign. Foldetta results are unavailable, so they do not influence the assessment. Overall, the collective evidence points to a benign effect for E63D, and this conclusion does not conflict with ClinVar, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.429200	Structured	0.474807	Uncertain	0.494	0.739	0.125											-3.821	Likely Benign	0.594	Likely Pathogenic	Likely Benign										0.066	Likely Benign	-0.83	Neutral	0.267	Benign	0.585	Possibly Damaging	3.98	Benign	0.00	Affected			0.1524	0.4130		3	2	0.0	-14.03
c.1901C>G	A634G 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant A634G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL, SIFT, FATHMM, and AlphaMissense‑Optimized, while pathogenic calls are made by Rosetta, premPS, PROVEAN, both polyPhen‑2 versions, ESM1b, and AlphaMissense‑Default. FoldX and Foldetta give uncertain results. High‑accuracy assessments indicate AlphaMissense‑Optimized predicts benign, whereas the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic. Foldetta remains uncertain. Overall, the majority of tools lean toward pathogenicity, and the high‑accuracy consensus also supports a pathogenic interpretation. Therefore, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.085092	Structured	0.052058	Uncertain	0.932	0.242	0.000											-10.685	Likely Pathogenic	0.613	Likely Pathogenic	Likely Benign	1.63	Ambiguous	0.1	2.27	Destabilizing	1.95	Ambiguous	1.09	Destabilizing	0.418	Likely Benign	-3.98	Deleterious	0.997	Probably Damaging	0.990	Probably Damaging	2.69	Benign	0.15	Tolerated			0.2182	0.3187		1	0	-2.2	-14.03
c.190A>G	I64V 2D AIThe SynGAP1 missense variant I64V is reported as “Likely Benign” in ClinVar and is not listed in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized scores benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates likely benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of computational evidence supports a benign classification, and this is consistent with the ClinVar status (no conflicting pathogenic annotation). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.422041	Structured	0.475481	Uncertain	0.478	0.747	0.125											-2.616	Likely Benign	0.154	Likely Benign	Likely Benign										0.086	Likely Benign	0.12	Neutral	0.000	Benign	0.000	Benign	4.24	Benign	0.00	Affected			0.0994	0.3302		4	3	-0.3	-14.03
c.1918A>T	T640S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T640S is listed in ClinVar as Benign (ClinVar ID 2980241.0) and is present in the gnomAD database (gnomAD ID 6‑33441177‑A‑T). Prediction tools that agree on a benign effect include REVEL, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome; the only inconclusive result is from FoldX, which is treated as unavailable. High‑accuracy assessments confirm benignity: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is benign; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, is benign. Overall, the variant is most likely benign, and this conclusion is consistent with its ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.066181	Structured	0.137043	Uncertain	0.893	0.284	0.000					Benign		1	6-33441177-A-T	1	6.20e-7	-2.371	Likely Benign	0.062	Likely Benign	Likely Benign	-0.78	Ambiguous	0.1	0.43	Likely Benign	-0.18	Likely Benign	-0.30	Likely Benign	0.088	Likely Benign	0.92	Neutral	0.000	Benign	0.001	Benign	3.60	Benign	0.33	Tolerated	3.37	30	0.3406	0.3484		1	1	-0.1	-14.03
c.1919C>G	T640S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T640S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: AlphaMissense‑Default, AlphaMissense‑Optimized, ESM1b, FATHMM, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, premPS, Foldetta, Rosetta, REVEL, and the SGM‑Consensus score (Likely Benign) all classify the change as tolerated. No tool predicts pathogenicity; the only inconclusive result is from FoldX, which is listed as Uncertain. High‑accuracy methods corroborate the benign assessment: AlphaMissense‑Optimized predicts Benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) reports Benign. Consequently, the variant is most likely benign, and this conclusion does not contradict the ClinVar status, which has no entry for this change. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.066181	Structured	0.137043	Uncertain	0.893	0.284	0.000											-2.371	Likely Benign	0.062	Likely Benign	Likely Benign	-0.78	Ambiguous	0.1	0.43	Likely Benign	-0.18	Likely Benign	-0.30	Likely Benign	0.109	Likely Benign	0.92	Neutral	0.000	Benign	0.001	Benign	3.60	Benign	0.33	Tolerated	3.37	30	0.3406	0.3484		1	1	-0.1	-14.03
c.1929G>C	E643D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E643D is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, AlphaMissense‑Default, AlphaMissense‑Optimized, FATHMM, and polyPhen2_HumVar. Tools that predict a pathogenic effect are premPS, PROVEAN, polyPhen2_HumDiv, SIFT, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑vs‑2 split. Overall, the majority of predictions (8 benign vs. 5 pathogenic) support a benign classification. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.033407	Structured	0.215915	Uncertain	0.871	0.315	0.000											-8.083	Likely Pathogenic	0.223	Likely Benign	Likely Benign	0.46	Likely Benign	0.2	-0.34	Likely Benign	0.06	Likely Benign	1.09	Destabilizing	0.292	Likely Benign	-2.96	Deleterious	0.694	Possibly Damaging	0.064	Benign	2.98	Benign	0.01	Affected			0.2040	0.4276		3	2	0.0	-14.03
c.1929G>T	E643D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E643D is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, AlphaMissense‑Default, AlphaMissense‑Optimized, FATHMM, and polyPhen2_HumVar. Tools that predict a pathogenic effect are premPS, PROVEAN, polyPhen2_HumDiv, SIFT, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑vs‑2 split. Overall, the majority of predictions (8 benign vs. 5 pathogenic) support a benign classification. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.033407	Structured	0.215915	Uncertain	0.871	0.315	0.000											-8.083	Likely Pathogenic	0.223	Likely Benign	Likely Benign	0.46	Likely Benign	0.2	-0.34	Likely Benign	0.06	Likely Benign	1.09	Destabilizing	0.292	Likely Benign	-2.96	Deleterious	0.694	Possibly Damaging	0.064	Benign	2.98	Benign	0.01	Affected			0.2040	0.4276		3	2	0.0	-14.03
c.1936C>G	L646V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L646V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split assessment: benign predictions come from REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, AlphaMissense‑Optimized, and FATHMM, whereas pathogenic predictions arise from FoldX, Rosetta, premPS, SIFT, and ESM1b. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, resolves to “Likely Benign” (3 benign vs 1 pathogenic votes). High‑accuracy assessments further indicate AlphaMissense‑Optimized as benign, SGM‑Consensus as likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. Overall, the majority of tools, including the high‑accuracy methods, lean toward a benign effect, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.048328	Structured	0.303751	Uncertain	0.941	0.344	0.000											-8.995	Likely Pathogenic	0.332	Likely Benign	Likely Benign	3.82	Destabilizing	0.2	2.01	Destabilizing	2.92	Destabilizing	1.41	Destabilizing	0.125	Likely Benign	-1.40	Neutral	0.040	Benign	0.021	Benign	3.21	Benign	0.03	Affected			0.2200	0.3767		2	1	0.4	-14.03
c.1953G>C	E651D 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant E651D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen2_HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only polyPhen2_HumDiv predicts a pathogenic outcome. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized scores the variant as benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely benign effect; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also reports a benign prediction. No prediction tool or stability analysis is inconclusive. Based on the collective evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.088832	Structured	0.365409	Uncertain	0.955	0.340	0.000											-3.220	Likely Benign	0.231	Likely Benign	Likely Benign	0.16	Likely Benign	0.1	0.33	Likely Benign	0.25	Likely Benign	-0.29	Likely Benign	0.153	Likely Benign	-0.13	Neutral	0.906	Possibly Damaging	0.429	Benign	3.48	Benign	0.53	Tolerated			0.1813	0.3762		3	2	0.0	-14.03
c.1953G>T	E651D 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant E651D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen2_HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. Only polyPhen2_HumDiv predicts a pathogenic outcome. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized scores the variant as benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely benign effect; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also reports a benign prediction. No prediction tool or stability analysis is inconclusive or missing. Based on the collective evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.088832	Structured	0.365409	Uncertain	0.955	0.340	0.000											-3.220	Likely Benign	0.231	Likely Benign	Likely Benign	0.16	Likely Benign	0.1	0.33	Likely Benign	0.25	Likely Benign	-0.29	Likely Benign	0.153	Likely Benign	-0.13	Neutral	0.906	Possibly Damaging	0.429	Benign	3.48	Benign	0.53	Tolerated			0.1813	0.3762		3	2	0.0	-14.03
c.1957C>G	L653V 2D AIThe SynGAP1 missense variant L653V is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that classify the variant as benign include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are FoldX, Rosetta, and premPS, while ESM1b is inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. Overall, the majority of evidence points to a benign impact, and this does not contradict the ClinVar “Uncertain” classification. Thus, based on current predictions, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.049374	Structured	0.335213	Uncertain	0.963	0.332	0.000					Uncertain		1				-7.050	In-Between	0.301	Likely Benign	Likely Benign	3.28	Destabilizing	0.3	2.18	Destabilizing	2.73	Destabilizing	1.32	Destabilizing	0.146	Likely Benign	-2.25	Neutral	0.227	Benign	0.039	Benign	3.28	Benign	0.08	Tolerated			0.1436	0.3557		2	1	0.4	-14.03
c.1962G>C	E654D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E654D missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, SIFT, FATHMM, and polyPhen‑2 HumVar. Those that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, ESM1b, and AlphaMissense‑Default. Two tools give uncertain results: Rosetta and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the predictions are mixed, with a slight majority leaning toward benign, but the high‑accuracy tools conflict. The variant is most likely benign based on the aggregate predictions, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.026892	Structured	0.303029	Uncertain	0.957	0.311	0.000											-10.454	Likely Pathogenic	0.886	Likely Pathogenic	Ambiguous	0.44	Likely Benign	0.0	0.52	Ambiguous	0.48	Likely Benign	0.29	Likely Benign	0.166	Likely Benign	-2.87	Deleterious	0.906	Possibly Damaging	0.429	Benign	3.38	Benign	0.11	Tolerated			0.1678	0.2583		3	2	0.0	-14.03
c.1962G>T	E654D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E654D has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, SIFT, FATHMM, and polyPhen‑2 HumVar. Those that predict a pathogenic effect are SGM Consensus, PROVEAN, polyPhen‑2 HumDiv, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show that AlphaMissense‑Optimized is uncertain (treated as unavailable), SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic outcome, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a benign effect. No other folding‑stability results are available. Overall, the balance of evidence leans toward a benign interpretation, and this assessment does not contradict ClinVar status, which currently contains no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.026892	Structured	0.303029	Uncertain	0.957	0.311	0.000											-10.454	Likely Pathogenic	0.886	Likely Pathogenic	Ambiguous	0.44	Likely Benign	0.0	0.52	Ambiguous	0.48	Likely Benign	0.29	Likely Benign	0.166	Likely Benign	-2.87	Deleterious	0.906	Possibly Damaging	0.429	Benign	3.38	Benign	0.11	Tolerated			0.1678	0.2583		3	2	0.0	-14.03
c.1963C>G	L655V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L655V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: REVEL, premPS, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, PROVEAN, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely benign outcome. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, SGM‑Consensus indicates likely benign, while Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, yields an uncertain result. No tools predict pathogenicity, and the uncertain stability assessment does not alter the overall benign inference. Therefore, based on the available predictions, the variant is most likely benign, and this conclusion is consistent with the absence of a ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.015344	Structured	0.268808	Uncertain	0.961	0.274	0.000											-6.743	Likely Benign	0.127	Likely Benign	Likely Benign	0.78	Ambiguous	0.0	0.58	Ambiguous	0.68	Ambiguous	0.38	Likely Benign	0.058	Likely Benign	-0.62	Neutral	0.008	Benign	0.003	Benign	3.45	Benign	0.44	Tolerated			0.1551	0.3190		2	1	0.4	-14.03
c.1968A>C	E656D 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant E656D has no ClinVar entry and is not reported in gnomAD. Prediction tools show mixed results: benign predictions come from REVEL, FoldX, premPS, polyPhen‑2 HumVar, SIFT, and FATHMM, while pathogenic predictions arise from PROVEAN, polyPhen‑2 HumDiv, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts Pathogenic, SGM‑Consensus confirms Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is Uncertain. No evidence from Foldetta or Rosetta is available to refute pathogenicity. Overall, the majority of high‑confidence tools predict a pathogenic impact, and this is consistent with the absence of ClinVar annotation; there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.032017	Structured	0.242242	Uncertain	0.963	0.264	0.000											-11.992	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic	0.22	Likely Benign	0.1	1.02	Ambiguous	0.62	Ambiguous	0.39	Likely Benign	0.275	Likely Benign	-2.72	Deleterious	0.985	Probably Damaging	0.426	Benign	3.41	Benign	0.06	Tolerated			0.2052	0.4120		3	2	0.0	-14.03
c.1968A>T	E656D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E656D missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools cluster into two groups: benign calls (REVEL, FoldX, premPS, polyPhen‑2 HumVar, SIFT, FATHMM) and pathogenic calls (PROVEAN, polyPhen‑2 HumDiv, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized). The SGM‑Consensus score is “Likely Pathogenic,” while Foldetta and Rosetta outputs are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates pathogenicity, and Foldetta remains inconclusive. Overall, the majority of evidence points to a pathogenic effect, and this conclusion does not contradict any ClinVar status because none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.032017	Structured	0.242242	Uncertain	0.963	0.264	0.000											-11.992	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic	0.22	Likely Benign	0.1	1.02	Ambiguous	0.62	Ambiguous	0.39	Likely Benign	0.273	Likely Benign	-2.72	Deleterious	0.985	Probably Damaging	0.426	Benign	3.41	Benign	0.06	Tolerated			0.2052	0.4120		3	2	0.0	-14.03
c.1990T>G	L664V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L664V is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect include SGM‑Consensus, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Rosetta and Foldetta are uncertain, providing no definitive evidence. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, while the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic (3 pathogenic vs 1 benign). Foldetta’s stability prediction is uncertain. Overall, the majority of reliable tools predict a pathogenic impact. Therefore, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.100716	Structured	0.089318	Uncertain	0.937	0.339	0.000											-11.515	Likely Pathogenic	0.755	Likely Pathogenic	Likely Benign	2.01	Destabilizing	0.1	1.13	Ambiguous	1.57	Ambiguous	1.37	Destabilizing	0.378	Likely Benign	-2.99	Deleterious	0.993	Probably Damaging	0.776	Possibly Damaging	2.91	Benign	0.01	Affected			0.0984	0.2628		2	1	0.4	-14.03
c.1998G>C	E666D 2D 3DClick to see structure in 3D Viewer AISynGAP1 E666D is listed in ClinVar with an uncertain significance (ID 587483.0) and is not reported in gnomAD. Functional prediction tools show a mixed signal: benign calls come from REVEL, SIFT, FATHMM, AlphaMissense‑Optimized, and Rosetta; pathogenic calls come from premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as likely pathogenic. High‑accuracy assessments give AlphaMissense‑Optimized a benign prediction, while the SGM Consensus remains pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is inconclusive. Overall, the balance of evidence slightly favors a pathogenic interpretation, but the predictions are not unequivocal. Thus, the variant is most likely pathogenic according to the current computational data, and this does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.155435	Structured	0.086870	Uncertain	0.925	0.387	0.000					Uncertain		1				-8.820	Likely Pathogenic	0.704	Likely Pathogenic	Likely Benign	0.88	Ambiguous	0.0	0.37	Likely Benign	0.63	Ambiguous	1.05	Destabilizing	0.197	Likely Benign	-2.69	Deleterious	0.992	Probably Damaging	0.603	Possibly Damaging	3.43	Benign	0.06	Tolerated	3.38	28	0.1926	0.3092		3	2	0.0	-14.03	237.2	16.5	0.0	0.0	-0.3	0.1		X						Potentially Pathogenic	The carboxylate group of Glu666, located on the α-helix (res. Ser641-Glu666), is involved in a highly coordinated hydrogen-bonding network between residues from two α-helices (res. Ser641-Glu666 and res. Arg563-Glu578) and from the α-α loop connecting the two α-helices (res. Ser641-Glu666 and res. Leu685-Val699), such as Lys566, Thr672, and Asn669, in the WT simulations. In the variant simulations, the shorter side chain of Asp666 cannot maintain these interactions as efficiently as Glu666 in the WT, resulting in a less coordinated hydrogen-bond network.
c.1998G>T	E666D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E666D missense variant is not reported in ClinVar (ClinVar ID: None) and has no entry in gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, SIFT, FATHMM, Rosetta, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are SGM Consensus, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM Consensus (a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. FoldX alone is also uncertain, so these results are treated as unavailable. Overall, the balance of evidence leans toward a pathogenic impact for E666D, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.155435	Structured	0.086870	Uncertain	0.925	0.387	0.000											-8.820	Likely Pathogenic	0.704	Likely Pathogenic	Likely Benign	0.88	Ambiguous	0.0	0.37	Likely Benign	0.63	Ambiguous	1.05	Destabilizing	0.197	Likely Benign	-2.69	Deleterious	0.992	Probably Damaging	0.603	Possibly Damaging	3.43	Benign	0.06	Tolerated	3.38	28	0.1926	0.3092		3	2	0.0	-14.03	237.2	16.5	0.0	0.0	-0.3	0.1		X						Potentially Pathogenic	The carboxylate group of Glu666, located on the α-helix (res. Ser641-Glu666), is involved in a highly coordinated hydrogen-bonding network between residues from two α-helices (res. Ser641-Glu666 and res. Arg563-Glu578) and from the α-α loop connecting the two α-helices (res. Ser641-Glu666 and res. Leu685-Val699), such as Lys566, Thr672, and Asn669, in the WT simulations. In the variant simulations, the shorter side chain of Asp666 cannot maintain these interactions as efficiently as Glu666 in the WT, resulting in a less coordinated hydrogen-bond network.
c.1999A>G	I667V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 I667V missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. Only ESM1b predicts a pathogenic outcome; all other tools (FoldX, Rosetta, premPS, AlphaMissense‑Default, Foldetta) are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, while the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a benign majority vote. Foldetta’s stability prediction is uncertain. Overall, the preponderance of evidence points to a benign effect. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.142424	Structured	0.083597	Uncertain	0.927	0.379	0.000											-8.482	Likely Pathogenic	0.406	Ambiguous	Likely Benign	1.32	Ambiguous	0.0	1.06	Ambiguous	1.19	Ambiguous	0.85	Ambiguous	0.234	Likely Benign	-0.86	Neutral	0.341	Benign	0.052	Benign	3.35	Benign	0.15	Tolerated			0.1178	0.3059		4	3	-0.3	-14.03
c.199C>G	L67V 2D AIThe SynGAP1 missense variant L67V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. In contrast, polyPhen‑2 HumDiv and SIFT predict pathogenic. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for the L67V substitution, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.458154	Structured	0.473668	Uncertain	0.428	0.761	0.125											-3.617	Likely Benign	0.285	Likely Benign	Likely Benign										0.122	Likely Benign	-0.31	Neutral	0.458	Possibly Damaging	0.364	Benign	4.15	Benign	0.00	Affected			0.1138	0.2817		2	1	0.4	-14.03
c.2008C>G	L670V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense change L670V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score all indicate benign. Only ESM1b predicts pathogenicity, while FoldX, Rosetta, and Foldetta provide uncertain or inconclusive stability results. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized is benign; the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is benign; and Foldetta remains uncertain. Taken together, the overwhelming majority of evidence supports a benign interpretation, and this conclusion does not conflict with the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.161087	Structured	0.090855	Uncertain	0.812	0.385	0.000											-9.829	Likely Pathogenic	0.113	Likely Benign	Likely Benign	1.45	Ambiguous	0.1	1.05	Ambiguous	1.25	Ambiguous	0.15	Likely Benign	0.025	Likely Benign	-0.60	Neutral	0.127	Benign	0.023	Benign	3.67	Benign	0.74	Tolerated			0.1558	0.4108		2	1	0.4	-14.03
c.2014A>T	T672S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T672S is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess pathogenicity uniformly indicate a benign effect: REVEL, FoldX, Rosetta, Foldetta, premPS (uncertain), PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign or likely benign. No tool predicts pathogenicity. High‑accuracy methods corroborate this: AlphaMissense‑Optimized reports benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields “Likely Benign”; and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts benign. Consequently, the variant is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.116183	Structured	0.102069	Uncertain	0.586	0.362	0.000											-4.932	Likely Benign	0.097	Likely Benign	Likely Benign	-0.13	Likely Benign	0.1	0.29	Likely Benign	0.08	Likely Benign	0.61	Ambiguous	0.044	Likely Benign	-2.32	Neutral	0.006	Benign	0.010	Benign	3.43	Benign	0.09	Tolerated			0.3005	0.4282		1	1	-0.1	-14.03
c.2017C>G	L673V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L673V is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic outcome are FoldX, Rosetta, Foldetta, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as Likely Benign, and Foldetta as pathogenic, yielding one pathogenic versus two benign predictions. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.060549	Structured	0.104692	Uncertain	0.545	0.369	0.000											-8.132	Likely Pathogenic	0.099	Likely Benign	Likely Benign	2.18	Destabilizing	0.3	2.10	Destabilizing	2.14	Destabilizing	0.10	Likely Benign	0.017	Likely Benign	-0.58	Neutral	0.016	Benign	0.003	Benign	3.36	Benign	0.28	Tolerated			0.1448	0.3777		2	1	0.4	-14.03
c.2020A>T	T674S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T674S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Functional prediction tools uniformly indicate a benign effect: SIFT, PolyPhen‑2 (HumDiv and HumVar), REVEL, PROVEAN, premPS, FoldX, Rosetta, and AlphaMissense‑Default all classify the change as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields “Likely Benign”; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also reports a benign effect. With all available evidence pointing to a benign outcome and no conflicting ClinVar annotation, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.129801	Structured	0.109297	Uncertain	0.521	0.349	0.000											-5.320	Likely Benign	0.082	Likely Benign	Likely Benign	-0.23	Likely Benign	0.0	0.44	Likely Benign	0.11	Likely Benign	-0.14	Likely Benign	0.084	Likely Benign	0.47	Neutral	0.107	Benign	0.033	Benign	3.47	Benign	1.00	Tolerated			0.3329	0.4938		1	1	-0.1	-14.03
c.2021C>G	T674S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T674S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Functional prediction tools uniformly indicate a benign effect: SIFT, PolyPhen‑2 (HumDiv and HumVar), REVEL, PROVEAN, premPS, FoldX, Rosetta, and AlphaMissense‑Default all classify the change as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields “Likely Benign”; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also reports a benign effect. With all available evidence pointing to a benign outcome and no conflicting ClinVar annotation, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.129801	Structured	0.109297	Uncertain	0.521	0.349	0.000											-5.320	Likely Benign	0.082	Likely Benign	Likely Benign	-0.23	Likely Benign	0.0	0.44	Likely Benign	0.11	Likely Benign	-0.14	Likely Benign	0.088	Likely Benign	0.47	Neutral	0.107	Benign	0.033	Benign	3.47	Benign	1.00	Tolerated			0.3329	0.4938		1	1	-0.1	-14.03
c.202C>G	L68V 2D AIThe SynGAP1 missense variant L68V has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT, while AlphaMissense‑Default remains uncertain. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized independently predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.534167	Disordered	0.470567	Uncertain	0.405	0.768	0.250											-4.079	Likely Benign	0.470	Ambiguous	Likely Benign										0.028	Likely Benign	-0.43	Neutral	0.458	Possibly Damaging	0.364	Benign	4.13	Benign	0.00	Affected			0.1077	0.2817		2	1	0.4	-14.03
c.2040G>C	E680D 2D AIThe SynGAP1 missense variant E680D is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify it as benign. Only polyPhen‑2 HumDiv predicts a pathogenic outcome. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized is benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) is benign. No prediction or folding stability result is missing or inconclusive. Based on the collective evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.209395	Structured	0.136843	Uncertain	0.636	0.320	0.000											-5.019	Likely Benign	0.289	Likely Benign	Likely Benign	0.21	Likely Benign	0.8	0.27	Likely Benign	0.24	Likely Benign	-0.10	Likely Benign	0.121	Likely Benign	-0.64	Neutral	0.906	Possibly Damaging	0.295	Benign	3.66	Benign	0.32	Tolerated			0.2199	0.5208		3	2	0.0	-14.03
c.2040G>T	E680D 2D AIThe SynGAP1 missense variant E680D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign or likely benign. Only polyPhen‑2 HumDiv flags the variant as pathogenic, representing the sole discordant prediction. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Benign; and Foldetta (combining FoldX‑MD and Rosetta outputs) is benign. No prediction or folding‑stability result is missing or inconclusive. **Based on the aggregate predictions, the variant is most likely benign, and this conclusion is not contradicted by any ClinVar status.** Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.209395	Structured	0.136843	Uncertain	0.636	0.320	0.000											-5.019	Likely Benign	0.289	Likely Benign	Likely Benign	0.21	Likely Benign	0.8	0.27	Likely Benign	0.24	Likely Benign	-0.10	Likely Benign	0.121	Likely Benign	-0.64	Neutral	0.906	Possibly Damaging	0.295	Benign	3.66	Benign	0.32	Tolerated			0.2199	0.5208		3	2	0.0	-14.03
c.2047A>G	I683V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I683V is listed in ClinVar with an uncertain significance and is present in gnomAD (6‑33441306‑A‑G). Across a panel of in silico predictors, the majority indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (derived from a majority of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Only polyPhen‑2 HumDiv classifies the change as pathogenic. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, the SGM‑Consensus (majority vote) is benign, and Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, is inconclusive and therefore not considered evidence. No other tool provides a pathogenic signal. Consequently, the variant is most likely benign, and this assessment does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.200174	Structured	0.143268	Uncertain	0.848	0.314	0.000					Uncertain		1	6-33441306-A-G	2	1.24e-6	-7.588	In-Between	0.138	Likely Benign	Likely Benign	0.90	Ambiguous	0.0	0.60	Ambiguous	0.75	Ambiguous	0.76	Ambiguous	0.112	Likely Benign	-0.78	Neutral	0.538	Possibly Damaging	0.080	Benign	3.35	Benign	0.14	Tolerated	3.42	17	0.1021	0.2898		4	3	-0.3	-14.03	215.6	29.1	0.0	0.0	-0.7	0.1						X		Potentially Benign	The sec-butyl side chain of Ile683, located in an entangled α-α loop connecting the two α-helices (res. Ser641-Glu666 and res. Leu685-Val699), is sterically packed against His453 and Glu688. In the variant simulations, the iso-propyl side chain of Val683 has similar size and physicochemical properties as Ile630 in the WT, and thus, it is able to maintain similar interactions in the inter-helix space. Consequently, no negative structural effects are observed during the simulations due to the residue swap.
c.2053T>G	L685V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L685V is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas a majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic effect. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM Consensus as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. No other folding‑stability methods provide definitive evidence. Overall, the preponderance of pathogenic predictions, including the SGM Consensus, suggests that the variant is most likely pathogenic; this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.175930	Structured	0.162061	Uncertain	0.913	0.280	0.000											-11.418	Likely Pathogenic	0.935	Likely Pathogenic	Ambiguous	1.87	Ambiguous	0.0	1.15	Ambiguous	1.51	Ambiguous	0.97	Ambiguous	0.214	Likely Benign	-2.99	Deleterious	0.993	Probably Damaging	0.694	Possibly Damaging	3.33	Benign	0.02	Affected			0.1414	0.3010		2	1	0.4	-14.03
c.205A>G	I69V 2D AIThe SynGAP1 missense variant I69V is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while the single pathogenic call comes from SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” status. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise indicates benign; Foldetta results are not available. Overall, the consensus of the available predictions indicates that the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.575842	Disordered	0.466129	Uncertain	0.437	0.786	0.375											-2.809	Likely Benign	0.176	Likely Benign	Likely Benign										0.080	Likely Benign	0.06	Neutral	0.267	Benign	0.141	Benign	4.24	Benign	0.00	Affected			0.0972	0.3142		4	3	-0.3	-14.03
c.2064G>C	E688D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E688D is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM. Tools that predict a pathogenic effect include SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain or inconclusive results come from FoldX, Rosetta, Foldetta, and premPS. High‑accuracy methods specifically give AlphaMissense‑Optimized a pathogenic prediction, SGM‑Consensus a pathogenic prediction, and Foldetta an uncertain result. Overall, the majority of evidence points to a pathogenic impact. This conclusion is not contradicted by ClinVar status, which currently has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.061840	Structured	0.211124	Uncertain	0.947	0.223	0.000											-11.890	Likely Pathogenic	0.987	Likely Pathogenic	Likely Pathogenic	1.79	Ambiguous	0.5	0.53	Ambiguous	1.16	Ambiguous	0.91	Ambiguous	0.302	Likely Benign	-2.89	Deleterious	0.995	Probably Damaging	0.960	Probably Damaging	3.47	Benign	0.08	Tolerated			0.1722	0.3492		3	2	0.0	-14.03
c.2064G>T	E688D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E688D is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM. Tools that predict a pathogenic effect include SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain or inconclusive results come from FoldX, Rosetta, Foldetta, and premPS. High‑accuracy methods specifically give: AlphaMissense‑Optimized – pathogenic; SGM‑Consensus – pathogenic; Foldetta – uncertain. Taken together, the majority of evidence points to a pathogenic impact. This conclusion is not contradicted by ClinVar status, which currently contains no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.061840	Structured	0.211124	Uncertain	0.947	0.223	0.000											-11.890	Likely Pathogenic	0.987	Likely Pathogenic	Likely Pathogenic	1.79	Ambiguous	0.5	0.53	Ambiguous	1.16	Ambiguous	0.91	Ambiguous	0.302	Likely Benign	-2.89	Deleterious	0.995	Probably Damaging	0.960	Probably Damaging	3.47	Benign	0.08	Tolerated			0.1722	0.3492		3	2	0.0	-14.03
c.2065C>G	L689V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L689V is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL and FATHMM, whereas the majority of other in silico predictors (FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) and the SGM Consensus (Likely Pathogenic) predict a pathogenic impact. The high‑accuracy methods give the following results: AlphaMissense‑Optimized is uncertain; SGM Consensus is Likely Pathogenic; Foldetta predicts a pathogenic effect. Taken together, the preponderance of evidence points to a pathogenic effect for L689V. This conclusion is not contradicted by ClinVar status, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.042364	Structured	0.227227	Uncertain	0.963	0.248	0.000											-11.387	Likely Pathogenic	0.862	Likely Pathogenic	Ambiguous	2.98	Destabilizing	0.1	2.25	Destabilizing	2.62	Destabilizing	1.32	Destabilizing	0.234	Likely Benign	-2.97	Deleterious	0.926	Possibly Damaging	0.481	Possibly Damaging	3.27	Benign	0.00	Affected			0.1393	0.3189		2	1	0.4	-14.03
c.2071A>T	T691S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T691S is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b; premPS is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Based on the overall consensus of the available predictions, the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.060549	Structured	0.271308	Uncertain	0.941	0.232	0.000											-9.274	Likely Pathogenic	0.123	Likely Benign	Likely Benign	0.44	Likely Benign	0.1	0.23	Likely Benign	0.34	Likely Benign	0.88	Ambiguous	0.041	Likely Benign	-1.67	Neutral	0.860	Possibly Damaging	0.584	Possibly Damaging	3.49	Benign	0.61	Tolerated			0.2213	0.3343		1	1	-0.1	-14.03
c.2074C>G	L692V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L692V is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized. All other evaluated tools—SGM‑Consensus, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default—predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized indicates benign, but the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) resolves as pathogenic, and Foldetta also predicts pathogenic. No predictions are missing or inconclusive. Overall, the preponderance of evidence points to a pathogenic effect for the variant, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.064632	Structured	0.295225	Uncertain	0.966	0.243	0.000											-11.441	Likely Pathogenic	0.733	Likely Pathogenic	Likely Benign	3.29	Destabilizing	0.1	2.91	Destabilizing	3.10	Destabilizing	1.57	Destabilizing	0.286	Likely Benign	-2.99	Deleterious	0.978	Probably Damaging	0.606	Possibly Damaging	3.12	Benign	0.01	Affected			0.1395	0.2460		2	1	0.4	-14.03
c.2081C>G	A694G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A694G is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. Predictions that are inconclusive or unavailable are FoldX, Rosetta, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely benign, and Foldetta as uncertain. Overall, the majority of evidence points to a benign impact. The variant’s predicted benign status does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.127496	Structured	0.352199	Uncertain	0.938	0.269	0.000											-3.420	Likely Benign	0.144	Likely Benign	Likely Benign	0.86	Ambiguous	0.0	1.16	Ambiguous	1.01	Ambiguous	0.86	Ambiguous	0.093	Likely Benign	-1.90	Neutral	0.866	Possibly Damaging	0.171	Benign	3.50	Benign	0.05	Affected			0.2015	0.3387		1	0	-2.2	-14.03
c.2083C>G	L695V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L695V is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b. FoldX, Rosetta, and Foldetta give uncertain results and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs. 2 pathogenic), and Foldetta is also unavailable. Overall, the majority of available predictions (six pathogenic vs. four benign) indicate that the variant is most likely pathogenic, and this assessment does not contradict the current ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.118441	Structured	0.373419	Uncertain	0.942	0.258	0.000											-10.605	Likely Pathogenic	0.317	Likely Benign	Likely Benign	1.61	Ambiguous	0.0	1.57	Ambiguous	1.59	Ambiguous	1.19	Destabilizing	0.274	Likely Benign	-2.99	Deleterious	0.993	Probably Damaging	0.694	Possibly Damaging	3.20	Benign	0.02	Affected			0.1158	0.2828		2	1	0.4	-14.03
c.2086C>G	L696V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 L696V variant is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that indicate a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized, whereas the majority of other in silico predictors (FoldX, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) report a pathogenic outcome; Rosetta remains inconclusive. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts benign, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—leans pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenic. Overall, the preponderance of evidence points to a pathogenic effect for the variant, which does not contradict the current ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.200174	Structured	0.390093	Uncertain	0.962	0.267	0.000					Uncertain		1				-11.909	Likely Pathogenic	0.745	Likely Pathogenic	Likely Benign	2.35	Destabilizing	0.1	1.85	Ambiguous	2.10	Destabilizing	1.46	Destabilizing	0.351	Likely Benign	-2.79	Deleterious	0.992	Probably Damaging	0.970	Probably Damaging	3.16	Benign	0.00	Affected	3.46	13	0.1307	0.2830		1	2	0.4	-14.03
c.2094G>C	E698D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E698D is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is benign; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts benign. No predictions are missing or inconclusive. Based on the collective evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar status because no ClinVar assertion exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.120615	Structured	0.417514	Uncertain	0.922	0.315	0.000											-6.716	Likely Benign	0.207	Likely Benign	Likely Benign	0.21	Likely Benign	0.1	0.35	Likely Benign	0.28	Likely Benign	0.16	Likely Benign	0.155	Likely Benign	-2.45	Neutral	0.977	Probably Damaging	0.921	Probably Damaging	3.35	Benign	0.03	Affected			0.1643	0.2597		3	2	0.0	-14.03
c.2094G>T	E698D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E698D is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is benign; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts benign. No predictions are missing or inconclusive. Based on the collective evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar status because no ClinVar assertion exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.120615	Structured	0.417514	Uncertain	0.922	0.315	0.000											-6.716	Likely Benign	0.207	Likely Benign	Likely Benign	0.21	Likely Benign	0.1	0.35	Likely Benign	0.28	Likely Benign	0.16	Likely Benign	0.155	Likely Benign	-2.45	Neutral	0.977	Probably Damaging	0.921	Probably Damaging	3.35	Benign	0.03	Affected			0.1643	0.2597		3	2	0.0	-14.03
c.2098C>G	L700V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L700V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates a likely benign outcome. In contrast, protein‑stability methods predict a deleterious impact: FoldX and Rosetta both score the variant as pathogenic, and the combined Foldetta analysis (FoldX‑MD + Rosetta) also reports a pathogenic effect. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely benign, while Foldetta remains pathogenic. Overall, the majority of predictions support a benign classification, and this is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.113710	Structured	0.416255	Uncertain	0.927	0.331	0.000											-3.703	Likely Benign	0.192	Likely Benign	Likely Benign	2.52	Destabilizing	0.0	3.16	Destabilizing	2.84	Destabilizing	0.13	Likely Benign	0.056	Likely Benign	0.37	Neutral	0.003	Benign	0.005	Benign	3.46	Benign	0.76	Tolerated			0.1424	0.2460		2	1	0.4	-14.03
c.2107C>G	L703V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L703V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, polyPhen‑2 HumVar, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are FoldX, Rosetta, Foldetta, premPS, polyPhen‑2 HumDiv, SIFT, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. Because the variant is not present in ClinVar or gnomAD, there is no existing clinical classification to contradict. Overall, the majority of predictions and the two high‑accuracy benign assessments suggest the variant is most likely benign, although the Foldetta result indicates a potential pathogenic effect that warrants further functional investigation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.144935	Structured	0.388282	Uncertain	0.929	0.353	0.000											-10.086	Likely Pathogenic	0.301	Likely Benign	Likely Benign	2.32	Destabilizing	0.1	2.61	Destabilizing	2.47	Destabilizing	1.07	Destabilizing	0.080	Likely Benign	-2.22	Neutral	0.789	Possibly Damaging	0.352	Benign	3.19	Benign	0.00	Affected			0.1383	0.2621		2	1	0.4	-14.03
c.2118A>C	E706D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E706D is not reported in ClinVar and is absent from gnomAD. All available in‑silico predictors classify it as benign: REVEL, FoldX, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the consensus SGM score (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all indicate a benign effect. No tool predicts pathogenicity. High‑accuracy assessments likewise support a benign outcome: AlphaMissense‑Optimized is benign, the SGM Consensus is “Likely Benign,” and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign stability. **Thus, the variant is most likely benign, and this prediction does not contradict any ClinVar status (none is available).** Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.200174	Structured	0.377033	Uncertain	0.929	0.363	0.000											-4.216	Likely Benign	0.087	Likely Benign	Likely Benign	0.22	Likely Benign	0.0	0.02	Likely Benign	0.12	Likely Benign	-0.16	Likely Benign	0.182	Likely Benign	-0.01	Neutral	0.000	Benign	0.000	Benign	4.17	Benign	0.41	Tolerated			0.1681	0.2726		3	2	0.0	-14.03
c.2118A>T	E706D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E706D is not reported in ClinVar and is absent from gnomAD. All available in‑silico predictors classify it as benign: REVEL, FoldX, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the consensus SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). No tool predicts pathogenicity. High‑accuracy assessments further support a benign effect: AlphaMissense‑Optimized predicts benign, the SGM Consensus indicates “Likely Benign,” and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts benign. With all evidence pointing to a neutral impact and no conflicting ClinVar annotation, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.200174	Structured	0.377033	Uncertain	0.929	0.363	0.000											-4.216	Likely Benign	0.087	Likely Benign	Likely Benign	0.22	Likely Benign	0.0	0.02	Likely Benign	0.12	Likely Benign	-0.16	Likely Benign	0.182	Likely Benign	-0.01	Neutral	0.000	Benign	0.000	Benign	4.17	Benign	0.41	Tolerated			0.1681	0.2726		3	2	0.0	-14.03
c.2120C>G	A707G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 A707G missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict a pathogenic outcome are PROVEAN, polyPhen‑2 (HumDiv and HumVar), and SIFT. The remaining tools (FoldX, Rosetta, Foldetta, premPS, ESM1b) give uncertain or inconclusive results and are treated as unavailable evidence. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also resolves to benign, while Foldetta remains uncertain. Overall, the majority of definitive predictions lean toward a benign effect, and there is no ClinVar status to contradict this assessment. Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.203355	Structured	0.371229	Uncertain	0.927	0.365	0.000											-7.480	In-Between	0.224	Likely Benign	Likely Benign	1.45	Ambiguous	0.0	1.52	Ambiguous	1.49	Ambiguous	0.62	Ambiguous	0.198	Likely Benign	-2.60	Deleterious	0.991	Probably Damaging	0.960	Probably Damaging	3.42	Benign	0.01	Affected			0.1678	0.2388		1	0	-2.2	-14.03
c.2122C>G	L708V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L708V is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome; the only inconclusive results are from FoldX (uncertain) and Foldetta (uncertain). High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also predicts benign, while Foldetta remains uncertain. Overall, the evidence strongly indicates that the variant is most likely benign, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.250310	Structured	0.365875	Uncertain	0.931	0.378	0.000											-4.361	Likely Benign	0.097	Likely Benign	Likely Benign	1.59	Ambiguous	0.0	0.12	Likely Benign	0.86	Ambiguous	-0.02	Likely Benign	0.122	Likely Benign	-0.23	Neutral	0.158	Benign	0.035	Benign	3.35	Benign	0.94	Tolerated			0.1094	0.2460		2	1	0.4	-14.03
c.2125C>G	L709V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L709V is not reported in ClinVar and is absent from gnomAD. Across the available in‑silico predictors, every tool that produced a definitive call classifies the variant as benign: REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all return benign scores. No tool predicts pathogenicity. The only inconclusive results are FoldX (uncertain) and Foldetta (uncertain), which are treated as unavailable evidence. High‑accuracy assessments reinforce the benign prediction: AlphaMissense‑Optimized is benign; the SGM‑Consensus, derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is also benign; Foldetta remains uncertain. Consequently, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.243554	Structured	0.365830	Uncertain	0.934	0.379	0.000											-4.406	Likely Benign	0.101	Likely Benign	Likely Benign	0.75	Ambiguous	0.0	0.42	Likely Benign	0.59	Ambiguous	0.03	Likely Benign	0.063	Likely Benign	-0.36	Neutral	0.062	Benign	0.016	Benign	3.42	Benign	0.45	Tolerated			0.1162	0.2460		2	1	0.4	-14.03
c.2131C>G	L711V 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L711V is listed in ClinVar with an uncertain significance and is present in gnomAD (ID 6‑33441596‑C‑G). Prediction tools that indicate a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized. The majority of other in silico predictors—FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default—classify the change as pathogenic, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports it as likely pathogenic. High‑accuracy assessments further show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. Overall, the preponderance of evidence points to a pathogenic effect, which does not conflict with the ClinVar designation of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.308712	Structured	0.377436	Uncertain	0.950	0.364	0.000					Uncertain		1	6-33441596-C-G	1	6.20e-7	-10.045	Likely Pathogenic	0.709	Likely Pathogenic	Likely Benign	3.48	Destabilizing	0.1	2.22	Destabilizing	2.85	Destabilizing	1.40	Destabilizing	0.170	Likely Benign	-2.59	Deleterious	0.992	Probably Damaging	0.970	Probably Damaging	3.34	Benign	0.00	Affected	3.50	9	0.1318	0.3010		1	2	0.4	-14.03
c.2140C>G	L714V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L714V has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect include FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 pathogenic vs. 2 benign). Overall, the majority of predictions (10 pathogenic vs. 4 benign) indicate a likely pathogenic impact. This conclusion is not contradicted by ClinVar status, which has no record for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.314870	Structured	0.402311	Uncertain	0.961	0.369	0.000											-4.966	Likely Benign	0.781	Likely Pathogenic	Likely Benign	3.91	Destabilizing	0.1	6.19	Destabilizing	5.05	Destabilizing	1.21	Destabilizing	0.259	Likely Benign	-2.76	Deleterious	0.995	Probably Damaging	0.970	Probably Damaging	3.16	Benign	0.00	Affected			0.1421	0.2689		2	1	0.4	-14.03
c.2149C>G	L717V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L717V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Benign). Two tools predict a damaging effect: polyPhen‑2 HumDiv and polyPhen‑2 HumVar. Stability‑based methods (FoldX, Rosetta, Foldetta) return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus as Likely Benign, and Foldetta as inconclusive. Taken together, the majority of evidence points to a benign impact. This conclusion is consistent with the absence of a ClinVar assertion, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.239899	Structured	0.429342	Uncertain	0.969	0.397	0.000											-6.164	Likely Benign	0.308	Likely Benign	Likely Benign	1.53	Ambiguous	0.0	1.25	Ambiguous	1.39	Ambiguous	0.09	Likely Benign	0.119	Likely Benign	-0.25	Neutral	0.995	Probably Damaging	0.970	Probably Damaging	3.38	Benign	0.51	Tolerated			0.1226	0.2489		2	1	0.4	-14.03
c.2152C>G	L718V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L718V is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL and AlphaMissense‑Optimized, whereas the remaining tools (FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default) all predict a pathogenic outcome. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized reports benign, the SGM Consensus (derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Based on the preponderance of pathogenic predictions and the high‑accuracy consensus, the variant is most likely pathogenic; this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.298791	Structured	0.438417	Uncertain	0.966	0.385	0.000											-11.585	Likely Pathogenic	0.693	Likely Pathogenic	Likely Benign	3.15	Destabilizing	0.1	2.11	Destabilizing	2.63	Destabilizing	1.14	Destabilizing	0.237	Likely Benign	-2.83	Deleterious	0.998	Probably Damaging	0.992	Probably Damaging	1.36	Pathogenic	0.00	Affected			0.1485	0.2656		2	1	0.4	-14.03
c.2161A>G	I721V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I721V is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. Predictions that are uncertain or inconclusive are FoldX, Rosetta, Foldetta, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus as benign, while Foldetta (combining FoldX‑MD and Rosetta outputs) remains uncertain. Overall, the majority of reliable predictors classify the variant as benign, and this conclusion does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.394753	Structured	0.454550	Uncertain	0.957	0.437	0.125											-6.730	Likely Benign	0.380	Ambiguous	Likely Benign	1.22	Ambiguous	0.0	1.11	Ambiguous	1.17	Ambiguous	0.48	Likely Benign	0.098	Likely Benign	-0.40	Neutral	0.969	Probably Damaging	0.960	Probably Damaging	2.60	Benign	0.45	Tolerated			0.0976	0.3070		4	3	-0.3	-14.03
c.2167A>T	T723S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T723S is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate benign or tolerated. Only two tools, polyPhen‑2 HumDiv and HumVar, predict a pathogenic outcome. The high‑accuracy consensus methods confirm the benign assessment: AlphaMissense‑Optimized scores benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta) predicts benign stability. Overall, the majority of evidence supports a benign impact for T723S, and this conclusion is consistent with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.476583	Structured	0.458243	Uncertain	0.945	0.447	0.375											-4.792	Likely Benign	0.091	Likely Benign	Likely Benign	-0.26	Likely Benign	0.0	0.28	Likely Benign	0.01	Likely Benign	0.23	Likely Benign	0.037	Likely Benign	-0.89	Neutral	0.673	Possibly Damaging	0.678	Possibly Damaging	3.55	Benign	0.06	Tolerated			0.3171	0.3731		1	1	-0.1	-14.03
c.2171C>G	A724G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A724G is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, SIFT, and AlphaMissense‑Optimized. Those that predict a pathogenic effect comprise SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default. Predictions from FoldX, Rosetta, Foldetta, and premPS are uncertain and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely pathogenic, and Foldetta as uncertain. Based on the overall distribution of predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.476583	Structured	0.458050	Uncertain	0.923	0.483	0.250											-8.908	Likely Pathogenic	0.580	Likely Pathogenic	Likely Benign	1.45	Ambiguous	0.1	1.73	Ambiguous	1.59	Ambiguous	0.56	Ambiguous	0.286	Likely Benign	-3.10	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	2.07	Pathogenic	0.08	Tolerated			0.2001	0.3609		1	0	-2.2	-14.03
c.2173C>G	L725V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L725V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL and AlphaMissense‑Optimized, while pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM. The remaining methods (FoldX, Rosetta, Foldetta, premPS, AlphaMissense‑Default) are inconclusive. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized predicts a benign effect, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely pathogenic outcome, and Foldetta provides no definitive stability change. Overall, the majority of evidence points toward a pathogenic impact, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.557691	Disordered	0.455613	Uncertain	0.911	0.491	0.625											-8.291	Likely Pathogenic	0.461	Ambiguous	Likely Benign	1.76	Ambiguous	0.1	1.87	Ambiguous	1.82	Ambiguous	0.77	Ambiguous	0.183	Likely Benign	-2.69	Deleterious	0.993	Probably Damaging	0.992	Probably Damaging	1.36	Pathogenic	0.01	Affected			0.1739	0.3977		2	1	0.4	-14.03
c.2188A>G	I730V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I730V is reported as “Likely Benign” in ClinVar and is not present in gnomAD. All available in‑silico predictors classify the change as benign: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields “Likely Benign”; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts benign. Consequently, the variant is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.733139	Disordered	0.420109	Uncertain	0.591	0.619	0.750											-3.960	Likely Benign	0.091	Likely Benign	Likely Benign	0.25	Likely Benign	0.1	0.04	Likely Benign	0.15	Likely Benign	0.03	Likely Benign	0.028	Likely Benign	-0.14	Neutral	0.112	Benign	0.033	Benign	3.48	Benign	0.39	Tolerated			0.1010	0.2303		4	3	-0.3	-14.03
c.2217G>C	E739D 2D AIThe SynGAP1 missense variant E739D is listed in ClinVar (ID 3661302.0) with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Only SIFT predicts a pathogenic outcome. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is “Likely Benign.” Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign effect, and this is not in conflict with the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.784345	Disordered	0.456400	Uncertain	0.313	0.834	0.875					Uncertain		1				-3.369	Likely Benign	0.062	Likely Benign	Likely Benign										0.097	Likely Benign	-0.49	Neutral	0.002	Benign	0.005	Benign	2.59	Benign	0.00	Affected			0.2145	0.4732		3	2	0.0	-14.03
c.2217G>T	E739D 2D AIIn silico analysis of the SynGAP1 E739D variant shows a consensus toward benign impact. Benign predictions come from SGM‑Consensus, REVEL, PROVEAN, polyPhen2_HumDiv, polyPhen2_HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized, whereas only SIFT predicts pathogenicity. High‑accuracy tools AlphaMissense‑Optimized and the SGM Consensus both classify the variant as benign; Foldetta results are unavailable. ClinVar has no entry for this variant and it is not present in gnomAD, so there is no conflicting evidence. Thus, the variant is most likely benign, and this assessment does not contradict ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.784345	Disordered	0.456400	Uncertain	0.313	0.834	0.875											-3.369	Likely Benign	0.062	Likely Benign	Likely Benign										0.097	Likely Benign	-0.49	Neutral	0.002	Benign	0.005	Benign	2.59	Benign	0.00	Affected			0.2145	0.4732		3	2	0.0	-14.03
c.2242C>G	L748V 2D AIThe SynGAP1 missense variant L748V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.703578	Disordered	0.611637	Binding	0.339	0.863	0.750											-3.454	Likely Benign	0.078	Likely Benign	Likely Benign										0.045	Likely Benign	-0.42	Neutral	0.679	Possibly Damaging	0.216	Benign	2.74	Benign	0.05	Affected			0.1680	0.3485		2	1	0.4	-14.03
c.2258C>G	A753G 2D AIThe SynGAP1 missense variant A753G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as benign. Only polyPhen‑2 HumDiv predicts a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign. Foldetta results are not available, so they do not influence the overall assessment. Based on the preponderance of evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.521092	Disordered	0.722781	Binding	0.381	0.873	0.625											-4.257	Likely Benign	0.090	Likely Benign	Likely Benign										0.071	Likely Benign	-1.10	Neutral	0.625	Possibly Damaging	0.192	Benign	2.62	Benign	0.65	Tolerated			0.2447	0.5089		1	0	-2.2	-14.03
c.225G>C	E75D 2D AIThe SynGAP1 missense variant E75D is reported in gnomAD (6‑33425833‑G‑C) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Only SIFT predicts a pathogenic outcome. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is “Likely Benign.” No Foldetta stability prediction is available. Overall, the preponderance of evidence indicates that E75D is most likely benign, and this conclusion is not contradicted by ClinVar status, which is currently absent. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.595080	Disordered	0.443881	Uncertain	0.303	0.822	0.500								6-33425833-G-C	1	6.20e-7	-3.710	Likely Benign	0.073	Likely Benign	Likely Benign										0.058	Likely Benign	-0.27	Neutral	0.001	Benign	0.000	Benign	4.25	Benign	0.00	Affected	4.32	1	0.2026	0.3833		2	3	0.0	-14.03
c.225G>T	E75D 2D AIThe SynGAP1 missense variant E75D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Based on the collective evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.595080	Disordered	0.443881	Uncertain	0.303	0.822	0.500											-3.710	Likely Benign	0.073	Likely Benign	Likely Benign										0.058	Likely Benign	-0.27	Neutral	0.001	Benign	0.000	Benign	4.25	Benign	0.00	Affected	4.32	1	0.2026	0.3833		2	3	0.0	-14.03
c.2262G>C	E754D 2D AIThe SynGAP1 missense variant E754D is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely benign outcome. No pathogenic predictions are present among the evaluated tools. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise indicates likely benign; Foldetta results are unavailable. Consequently, the variant is most likely benign based on the collective predictions, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.505461	Disordered	0.750531	Binding	0.357	0.872	0.500											-2.360	Likely Benign	0.065	Likely Benign	Likely Benign										0.076	Likely Benign	-0.27	Neutral	0.002	Benign	0.007	Benign	2.53	Benign	0.45	Tolerated			0.1725	0.3983		3	2	0.0	-14.03
c.2262G>T	E754D 2D AIThe SynGAP1 missense variant E754D is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely benign outcome. No pathogenic predictions are present among the evaluated tools. High‑accuracy assessments confirm this trend: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise indicates likely benign; Foldetta results are unavailable. Consequently, the variant is most likely benign based on current predictions, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.505461	Disordered	0.750531	Binding	0.357	0.872	0.500											-2.360	Likely Benign	0.065	Likely Benign	Likely Benign										0.076	Likely Benign	-0.27	Neutral	0.002	Benign	0.007	Benign	2.53	Benign	0.45	Tolerated			0.1725	0.3983		3	2	0.0	-14.03
c.2287C>G	L763V 2D AIThe SynGAP1 missense variant L763V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv indicates a pathogenic outcome, creating a single discordant signal. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also reports Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence supports a benign classification, and this conclusion is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.380708	Structured	0.918636	Binding	0.351	0.865	0.125											-5.138	Likely Benign	0.164	Likely Benign	Likely Benign										0.027	Likely Benign	-0.94	Neutral	0.573	Possibly Damaging	0.230	Benign	2.57	Benign	0.25	Tolerated			0.1548	0.2817		2	1	0.4	-14.03
c.2299A>G	I767V 2D AIThe SynGAP1 missense variant I767V is listed in ClinVar (ID 1402700.0) with an “Uncertain” clinical significance and is not reported in gnomAD. All evaluated in‑silico predictors classify the substitution as benign: REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all return benign scores. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a “Likely Benign” outcome. No tool predicts pathogenicity. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, SGM‑Consensus is likely benign, while Foldetta (combining FoldX‑MD and Rosetta stability predictions) has no available result for this variant. Overall, the computational evidence strongly supports a benign effect, and this conclusion does not contradict the current ClinVar status of uncertainty. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.321458	Structured	0.927771	Binding	0.369	0.872	0.125					Uncertain		1				-2.791	Likely Benign	0.064	Likely Benign	Likely Benign										0.096	Likely Benign	0.10	Neutral	0.072	Benign	0.029	Benign	4.21	Benign	1.00	Tolerated	3.64	6	0.1418	0.4227		4	3	-0.3	-14.03
c.22A>G	I8V 2D AIThe SynGAP1 missense variant I8V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign effect, and this assessment does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.490133	Structured	0.543080	Binding	0.341	0.916	0.625											-2.723	Likely Benign	0.081	Likely Benign	Likely Benign										0.122	Likely Benign	-0.01	Neutral	0.005	Benign	0.001	Benign	4.22	Benign	0.00	Affected			0.1031	0.3470		4	3	-0.3	-14.03
c.2305C>G	L769V 2D AIThe SynGAP1 missense variant L769V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv flags it as pathogenic, but this is the sole discordant call. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” consensus. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the preponderance of evidence indicates that the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.411940	Structured	0.928432	Binding	0.367	0.883	0.250											-4.585	Likely Benign	0.106	Likely Benign	Likely Benign										0.075	Likely Benign	-0.41	Neutral	0.625	Possibly Damaging	0.249	Benign	4.04	Benign	0.25	Tolerated			0.1364	0.2558		2	1	0.4	-14.03
c.2321C>G	A774G 2D AIThe SynGAP1 missense variant A774G is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Overall, the consensus of all available predictions points to a benign impact, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.450668	Structured	0.905168	Binding	0.336	0.897	0.250											-3.129	Likely Benign	0.099	Likely Benign	Likely Benign										0.056	Likely Benign	-0.68	Neutral	0.135	Benign	0.152	Benign	4.16	Benign	0.22	Tolerated			0.2392	0.5436		1	0	-2.2	-14.03
c.2329C>G	L777V 2D AIThe SynGAP1 missense variant L777V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect for the variant, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.408655	Structured	0.876129	Binding	0.336	0.882	0.250											-5.693	Likely Benign	0.134	Likely Benign	Likely Benign										0.084	Likely Benign	-1.05	Neutral	0.843	Possibly Damaging	0.920	Probably Damaging	4.07	Benign	0.05	Affected			0.1651	0.3977		2	1	0.4	-14.03
c.2351C>G	A784G 2D AIThe SynGAP1 missense variant A784G is reported in gnomAD (ID 6‑33442903‑C‑G) and has no ClinVar entry. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Benign.” Foldetta results are unavailable. Overall, the evidence strongly suggests the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.801317	Disordered	0.708872	Binding	0.314	0.896	0.625								6-33442903-C-G	1	6.20e-7	-3.370	Likely Benign	0.158	Likely Benign	Likely Benign										0.056	Likely Benign	-1.24	Neutral	0.224	Benign	0.138	Benign	2.67	Benign	0.26	Tolerated	3.64	6	0.2303	0.4418		0	1	-2.2	-14.03
c.2356C>G	L786V 2D AIThe SynGAP1 missense variant L786V is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact for this variant, and this conclusion does not contradict the ClinVar status, which currently has no classification for L786V. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.882776	Disordered	0.655253	Binding	0.341	0.895	0.750											-4.607	Likely Benign	0.310	Likely Benign	Likely Benign										0.099	Likely Benign	-1.66	Neutral	0.997	Probably Damaging	0.992	Probably Damaging	2.00	Pathogenic	0.00	Affected			0.1683	0.4049		2	1	0.4	-14.03
c.2368A>T	T790S 2D AIThe SynGAP1 missense variant T790S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized returns Benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Benign. No Foldetta stability data are available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect for T790S, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.964893	Disordered	0.509280	Binding	0.385	0.896	0.875											-3.914	Likely Benign	0.123	Likely Benign	Likely Benign										0.125	Likely Benign	-1.83	Neutral	0.997	Probably Damaging	0.989	Probably Damaging	2.39	Pathogenic	0.33	Tolerated	3.64	6	0.3416	0.4449		1	1	-0.1	-14.03
c.2369C>G	T790S 2D AIThe SynGAP1 missense variant T790S (ClinVar ID 1020340) is listed as Uncertain in ClinVar and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus, which is derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN. Pathogenic predictions come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict the ClinVar status of Uncertain. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.964893	Disordered	0.509280	Binding	0.385	0.896	0.875					Uncertain		2				-3.914	Likely Benign	0.123	Likely Benign	Likely Benign										0.134	Likely Benign	-1.83	Neutral	0.997	Probably Damaging	0.989	Probably Damaging	2.39	Pathogenic	0.33	Tolerated	3.64	6	0.3416	0.4449		1	1	-0.1	-14.03
c.2376A>C	E792D 2D AIThe SynGAP1 missense variant E792D is not reported in ClinVar and is absent from gnomAD. All evaluated in‑silico predictors classify the change as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all return benign scores. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign effect. No pathogenic predictions are present. High‑accuracy tools reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise predicts likely benign; Foldetta results are unavailable. Consequently, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.974374	Disordered	0.452261	Uncertain	0.352	0.896	0.875											-3.746	Likely Benign	0.089	Likely Benign	Likely Benign										0.091	Likely Benign	-1.06	Neutral	0.000	Benign	0.001	Benign	3.97	Benign	0.26	Tolerated			0.2096	0.5376		3	2	0.0	-14.03
c.2376A>T	E792D 2D AIThe SynGAP1 missense variant E792D is not reported in ClinVar and is absent from gnomAD. All evaluated in‑silico predictors classify the change as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all return benign scores. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign effect. No pathogenic predictions are present. High‑accuracy tools reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise predicts likely benign; Foldetta results are unavailable. Consequently, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.974374	Disordered	0.452261	Uncertain	0.352	0.896	0.875											-3.746	Likely Benign	0.089	Likely Benign	Likely Benign										0.091	Likely Benign	-1.06	Neutral	0.000	Benign	0.001	Benign	3.97	Benign	0.26	Tolerated			0.2096	0.5376		3	2	0.0	-14.03
c.2413C>G	L805V 2D AIThe SynGAP1 missense variant L805V is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess pathogenicity largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as benign. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority vote) is also benign. Foldetta results are not available, so they do not influence the conclusion. Overall, the preponderance of evidence indicates that the variant is most likely benign, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.775545	Disordered	0.827669	Binding	0.341	0.903	0.625											-2.445	Likely Benign	0.094	Likely Benign	Likely Benign										0.027	Likely Benign	-1.16	Neutral	0.003	Benign	0.008	Benign	2.65	Benign	0.00	Affected			0.1553	0.3493		2	1	0.4	-14.03
c.241C>G	L81V 2D AIThe SynGAP1 missense variant L81V is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as benign. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign status. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the preponderance of evidence supports a benign classification for L81V, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.632174	Disordered	0.502033	Binding	0.291	0.878	0.250											-5.207	Likely Benign	0.289	Likely Benign	Likely Benign										0.038	Likely Benign	-0.51	Neutral	0.178	Benign	0.014	Benign	4.04	Benign	0.00	Affected			0.1423	0.2653		2	1	0.4	-14.03
c.2437C>G	L813V 2D AIThe SynGAP1 missense variant L813V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only the two polyPhen‑2 implementations (HumDiv and HumVar) predict pathogenicity. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” consensus. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are not available. Based on the preponderance of evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.411940	Structured	0.838481	Binding	0.292	0.905	0.250											-4.809	Likely Benign	0.215	Likely Benign	Likely Benign										0.136	Likely Benign	-0.98	Neutral	0.994	Probably Damaging	0.856	Possibly Damaging	2.62	Benign	0.28	Tolerated			0.1704	0.3744		2	1	0.4	-14.03
c.2441C>G	A814G 2D AIThe SynGAP1 missense variant A814G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign) score; pathogenic predictions come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.411940	Structured	0.814830	Binding	0.368	0.902	0.250											-3.659	Likely Benign	0.312	Likely Benign	Likely Benign										0.071	Likely Benign	-1.83	Neutral	0.896	Possibly Damaging	0.649	Possibly Damaging	2.60	Benign	0.05	Affected			0.2336	0.4504		1	0	-2.2	-14.03
c.244C>G	L82V 2D AIThe SynGAP1 missense variant L82V is not reported in ClinVar (ClinVar status: not listed) but is present in gnomAD (ID 6‑33425852‑C‑G). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. Those that predict a pathogenic effect are SIFT and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain, and no Foldetta stability result is available. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments therefore indicate a benign likelihood: AlphaMissense‑Optimized is inconclusive, SGM‑Consensus is likely benign, and Foldetta data are missing. Overall, the majority of predictions support a benign impact, and this is consistent with the absence of a ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.637480	Disordered	0.517720	Binding	0.284	0.890	0.375								6-33425852-C-G			-6.701	Likely Benign	0.914	Likely Pathogenic	Ambiguous										0.065	Likely Benign	-1.13	Neutral	0.371	Benign	0.024	Benign	3.72	Benign	0.00	Affected	4.32	1	0.1467	0.2353		1	2	0.4	-14.03
c.2456C>G	A819G 2D AIThe SynGAP1 missense variant A819G is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic). Foldetta results are unavailable. Overall, the majority of predictions (six benign vs three pathogenic) support a benign classification. Thus, the variant is most likely benign, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.694846	Disordered	0.707644	Binding	0.317	0.892	0.625											-5.730	Likely Benign	0.714	Likely Pathogenic	Likely Benign										0.116	Likely Benign	-2.17	Neutral	0.104	Benign	0.121	Benign	2.29	Pathogenic	0.03	Affected			0.2363	0.5396		1	0	-2.2	-14.03
c.2464A>T	T822S 2D AIThe SynGAP1 missense variant T822S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact for T822S, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.724957	Disordered	0.651624	Binding	0.295	0.881	0.750											-1.710	Likely Benign	0.655	Likely Pathogenic	Likely Benign										0.107	Likely Benign	-0.54	Neutral	0.998	Probably Damaging	0.949	Probably Damaging	3.08	Benign	0.74	Tolerated			0.3794	0.4547		1	1	-0.1	-14.03
c.2479A>G	I827V 2D AIThe SynGAP1 missense variant I827V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is “Likely Benign”). In contrast, the two polyPhen‑2 implementations (HumDiv and HumVar) predict a pathogenic outcome. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is also likely benign. No Foldetta stability prediction is available, so it does not influence the assessment. Overall, the majority of evidence indicates that the I827V variant is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.590140	Disordered	0.636272	Binding	0.383	0.884	0.625											-3.590	Likely Benign	0.249	Likely Benign	Likely Benign										0.129	Likely Benign	0.05	Neutral	0.958	Probably Damaging	0.970	Probably Damaging	2.70	Benign	1.00	Tolerated			0.1011	0.2536		4	3	-0.3	-14.03
c.2482A>T	T828S 2D AIThe SynGAP1 missense variant T828S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is “Likely Benign”). In contrast, the two polyPhen‑2 implementations (HumDiv and HumVar) predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is also likely benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence indicates that T828S is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.604312	Disordered	0.631236	Binding	0.321	0.879	0.500											-2.851	Likely Benign	0.285	Likely Benign	Likely Benign										0.152	Likely Benign	-0.49	Neutral	0.999	Probably Damaging	0.992	Probably Damaging	2.67	Benign	0.52	Tolerated			0.3332	0.3913		1	1	-0.1	-14.03
c.2487G>C	E829D 2D AIThe SynGAP1 missense variant E829D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and FATHMM. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the preponderance of evidence from multiple independent predictors indicates that E829D is most likely benign, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.562014	Disordered	0.626045	Binding	0.326	0.882	0.375											-4.015	Likely Benign	0.091	Likely Benign	Likely Benign										0.066	Likely Benign	-1.89	Neutral	0.217	Benign	0.121	Benign	2.40	Pathogenic	0.00	Affected			0.1939	0.4964		3	2	0.0	-14.03
c.2487G>T	E829D 2D AIThe SynGAP1 missense variant E829D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and FATHMM. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the preponderance of evidence from multiple independent predictors indicates that E829D is most likely benign, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.562014	Disordered	0.626045	Binding	0.326	0.882	0.375											-4.015	Likely Benign	0.091	Likely Benign	Likely Benign										0.066	Likely Benign	-1.89	Neutral	0.217	Benign	0.121	Benign	2.40	Pathogenic	0.00	Affected			0.1939	0.4964		3	2	0.0	-14.03